NEW YORK (Reuters Health) - Results of recent experiments provide "definitive evidence" that human embryonic stem cells can be used to generate cells that secrete insulin in response to glucose, like the beta-cells in the pancreas.
"Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human beta-cells," Dr. Emmanuel E. Baetge and colleagues, from Novocell Inc. in San Diego, comment in the research journal Nature Biotechnology.
In the study, the researchers show that pancreatic tissue, derived from human embryonic stems cells, can generate cells that are "morphologically and functionally similar" to beta-cells after being implanted into mice.
In addition, the team goes on to show that implantation of the stem cell-derived tissue stops glucose levels rising excessively in the animals.
These findings suggest that human embryonic stem cells could, in fact, represent a renewable supply of insulin-producing cells for treating diabetes, the researchers conclude.
SOURCE: Nature Biotechnology, online February 20, 2008.
Monday, March 10, 2008
Repair joints
By Debra Sherman
SAN FRANCISCO (Reuters) - The orthopedics industry is using more biology and less metal to repair injured and diseased joints.
Researchers attending the annual meeting of the American Academy of Orthopaedic Surgeons in San Francisco this week said they are slowly unlocking the doors to regenerative medicine using stem cells, gene therapy and tissue engineering.
"It's the future of our specialty," said Dr. Thomas Einhorn, chairman of the Department of Orthopedic Surgery and professor of orthopedic surgery, biochemistry and biomedical engineering at Boston University.
Historically, the orthopedist's arsenal looked much like a carpenter's. It was dominated by heavy metal -- cages, screws, saws, drills and metal implants for joints such as hips and knees.
Stem cell therapy could eventually eliminate the need for joint replacement, said Einhorn, who last year performed his first hip replacement surgery using the patient's own stem cells.
The undifferentiated, unspecialized stem cells can morph into specialized cells with specific functions in the body. Adult stem cells are available from a number of sources, including bone marrow and fat.
Stem cells from a patient's own body are being used to repair bones, ligaments, cartilage, muscle, spinal cord and nerves.
In the hip replacement surgery, Einhorn extracted bone marrow from a middle-aged male patient, sent it to a lab that removed everything but the stem cells, then put the cells in a spray gun and coated the hip implant to induce rapid bone growth over the implant.
"I don't know if I'll see it in my career, but we're certainly moving that way. It might take 20 years before we can totally regenerate a joint that way," Einhorn said.
Dr. Scott Rodeo, co-chief of Sports Medicine and Shoulder Service at the Hospital for Special Surgery in New York and an associate team physician for the Super Bowl champion New York Giants, said animal studies suggest that stem cells and bone morphogenic proteins (BMPs) can be used to repair rotator cuff tears in the shoulder, a common sports injury that often requires surgery.
BMPs are a group of growth factors and cytokines known for their ability to induce the formation of bone and cartilage. They are sold by Medtronic Inc and Stryker Corp.
Stem cell therapy may also have applications in spine fusion, said Dr. Scott Boden of Emory Spine Center.
"We have a tougher time in the spine," he said, adding that it may just require more cells to form bone there.
Implanting BMPs may "attract other stem cells to the site and tell them to become bone cells," he said.
(Editing by John Wallace)
SAN FRANCISCO (Reuters) - The orthopedics industry is using more biology and less metal to repair injured and diseased joints.
Researchers attending the annual meeting of the American Academy of Orthopaedic Surgeons in San Francisco this week said they are slowly unlocking the doors to regenerative medicine using stem cells, gene therapy and tissue engineering.
"It's the future of our specialty," said Dr. Thomas Einhorn, chairman of the Department of Orthopedic Surgery and professor of orthopedic surgery, biochemistry and biomedical engineering at Boston University.
Historically, the orthopedist's arsenal looked much like a carpenter's. It was dominated by heavy metal -- cages, screws, saws, drills and metal implants for joints such as hips and knees.
Stem cell therapy could eventually eliminate the need for joint replacement, said Einhorn, who last year performed his first hip replacement surgery using the patient's own stem cells.
The undifferentiated, unspecialized stem cells can morph into specialized cells with specific functions in the body. Adult stem cells are available from a number of sources, including bone marrow and fat.
Stem cells from a patient's own body are being used to repair bones, ligaments, cartilage, muscle, spinal cord and nerves.
In the hip replacement surgery, Einhorn extracted bone marrow from a middle-aged male patient, sent it to a lab that removed everything but the stem cells, then put the cells in a spray gun and coated the hip implant to induce rapid bone growth over the implant.
"I don't know if I'll see it in my career, but we're certainly moving that way. It might take 20 years before we can totally regenerate a joint that way," Einhorn said.
Dr. Scott Rodeo, co-chief of Sports Medicine and Shoulder Service at the Hospital for Special Surgery in New York and an associate team physician for the Super Bowl champion New York Giants, said animal studies suggest that stem cells and bone morphogenic proteins (BMPs) can be used to repair rotator cuff tears in the shoulder, a common sports injury that often requires surgery.
BMPs are a group of growth factors and cytokines known for their ability to induce the formation of bone and cartilage. They are sold by Medtronic Inc and Stryker Corp.
Stem cell therapy may also have applications in spine fusion, said Dr. Scott Boden of Emory Spine Center.
"We have a tougher time in the spine," he said, adding that it may just require more cells to form bone there.
Implanting BMPs may "attract other stem cells to the site and tell them to become bone cells," he said.
(Editing by John Wallace)
Stem Cells Promise!
The Promise of Stem Cells
Studying stem cells will help us understand how they transform into the dazzling array of specialized cells that make us what we are. Some of the most serious medical conditions, such as cancer and birth defects, are due to problems that occur somewhere in this process. A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions.
Another potential application of stem cells is making cells and tissues for medical therapies. Today, donated organs and tissues are often used to replace those that are diseased or destroyed. Unfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantation. Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat a myriad of diseases, conditions, and disabilities including Parkinson's and Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid arthritis.
Have human embryonic stem cells successfully treated any human diseases?
Scientists have been able to do experiments with human embryonic stem cells (hESC) only since 1998, when a group led by Dr. James Thomson at the University of Wisconsin developed a technique to isolate and grow the cells. Moreover, Federal funds to support hESC research have been available since only August 9, 2001, when President Bush announced his decision on Federal funding for hESC research. Because many academic researchers rely on Federal funds to support their laboratories, they are just beginning to learn how to grow and use the cells. Thus, although hESC are thought to offer potential cures and therapies for many devastating diseases, research using them is still in its early stages.
Adult stem cells, such as blood-forming stem cells in bone marrow (called hematopoietic stem cells, or HSCs), are currently the only type of stem cell commonly used to treat human diseases. Doctors have been transferring HSCs in bone marrow transplants for over 40 years. More advanced techniques of collecting, or "harvesting," HSCs are now used in order to treat leukemia, lymphoma and several inherited blood disorders.
The clinical potential of adult stem cells has also been demonstrated in the treatment of other human diseases that include diabetes and advanced kidney cancer. However, these newer uses have involved studies with a very limited number of patients.
Studying stem cells will help us understand how they transform into the dazzling array of specialized cells that make us what we are. Some of the most serious medical conditions, such as cancer and birth defects, are due to problems that occur somewhere in this process. A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions.
Another potential application of stem cells is making cells and tissues for medical therapies. Today, donated organs and tissues are often used to replace those that are diseased or destroyed. Unfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantation. Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat a myriad of diseases, conditions, and disabilities including Parkinson's and Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid arthritis.
Have human embryonic stem cells successfully treated any human diseases?
Scientists have been able to do experiments with human embryonic stem cells (hESC) only since 1998, when a group led by Dr. James Thomson at the University of Wisconsin developed a technique to isolate and grow the cells. Moreover, Federal funds to support hESC research have been available since only August 9, 2001, when President Bush announced his decision on Federal funding for hESC research. Because many academic researchers rely on Federal funds to support their laboratories, they are just beginning to learn how to grow and use the cells. Thus, although hESC are thought to offer potential cures and therapies for many devastating diseases, research using them is still in its early stages.
Adult stem cells, such as blood-forming stem cells in bone marrow (called hematopoietic stem cells, or HSCs), are currently the only type of stem cell commonly used to treat human diseases. Doctors have been transferring HSCs in bone marrow transplants for over 40 years. More advanced techniques of collecting, or "harvesting," HSCs are now used in order to treat leukemia, lymphoma and several inherited blood disorders.
The clinical potential of adult stem cells has also been demonstrated in the treatment of other human diseases that include diabetes and advanced kidney cancer. However, these newer uses have involved studies with a very limited number of patients.
Sunday, March 9, 2008
Stem Cell Therapies Today
These include:
Adult Stem Cell Transplant: Bone Marrow Stem Cells
Adult Stem Cell Transplant: Peripheral Blood Stem Cells
Umbilical Cord Blood Stem Cell Transplant
Adult Stem Cell Transplant: Bone Marrow Stem Cells
Perhaps the best-known stem cell therapy to date is the bone marrow transplant, which is used to treat leukemia and other types of cancer, as well as various blood disorders.
Why is this a stem cell therapy?
Leukemia is a cancer of white blood cells, or leukocytes. Like other blood cells, leukocytes are made in the bone marrow through a process that begins with multipotent adult stem cells. Mature leukocytes are released into the bloodstream, where they work to fight off infections in our bodies.
Leukemia results when leukocytes begin to grow and function abnormally, becoming cancerous. These abnormal cells cannot fight off infection, and they interfere with the functions of other organs.
Successful treatment for leukemia depends on getting rid of all the abnormal leukocytes in the patient, allowing healthy ones to grow in their place. One way to do this is through chemotherapy, which uses potent drugs to target and kill the abnormal cells. When chemotherapy alone can't eliminate them all, physicians sometimes turn to bone marrow transplants.
In a bone marrow transplant, the patient's bone marrow stem cells are replaced with those from a healthy, matching donor. To do this, all of the patient's existing bone marrow and abnormal leukocytes are first killed using a combination of chemotherapy and radiation. Next, a sample of donor bone marrow containing healthy stem cells is introduced into the patient's bloodstream.
If the transplant is successful, the stem cells will migrate into the patient's bone marrow and begin producing new, healthy leukocytes to replace the abnormal cells.
Adult Stem Cell Transplant: Peripheral Blood Stem Cell Transplant
While most blood stem cells reside in the bone marrow, a small number are present in the bloodstream. These multipotent peripheral blood stem cells, or PBSCs, can be used just like bone marrow stem cells to treat leukemia, other cancers and various blood disorders. Since they can be obtained from drawn blood, PBSCs are easier to collect than bone marrow stem cells, which must be extracted from within bones. This makes PBSCs a less invasive treatment option than bone marrow stem cells. PBSCs are sparse in the bloodstream, however, so collecting enough to perform a transplant can pose a challenge.
Umbilical Cord Blood Stem Cell Transplant
Newborn infants no longer need their umbilical cords, so they have traditionally been discarded as a by-product of the birth process. In recent years, however, the multipotent-stem-cell-rich blood found in the umbilical cord has proven useful in treating the same types of health problems as those treated using bone marrow stem cells and PBSCs.
Umbilical cord blood stem cell transplants are less prone to rejection than either bone marrow or peripheral blood stem cells. This is probably because the cells have not yet developed the features that can be recognized and attacked by the recipient's immune system. Also, because umbilical cord blood lacks well-developed immune cells, there is less chance that the transplanted cells will attack the recipient's body, a problem called graft versus host disease.
Both the versatility and availability of umbilical cord blood stem cells makes them a potent resource for transplant therapies.
Adult Stem Cell Transplant: Bone Marrow Stem Cells
Adult Stem Cell Transplant: Peripheral Blood Stem Cells
Umbilical Cord Blood Stem Cell Transplant
Adult Stem Cell Transplant: Bone Marrow Stem Cells
Perhaps the best-known stem cell therapy to date is the bone marrow transplant, which is used to treat leukemia and other types of cancer, as well as various blood disorders.
Why is this a stem cell therapy?
Leukemia is a cancer of white blood cells, or leukocytes. Like other blood cells, leukocytes are made in the bone marrow through a process that begins with multipotent adult stem cells. Mature leukocytes are released into the bloodstream, where they work to fight off infections in our bodies.
Leukemia results when leukocytes begin to grow and function abnormally, becoming cancerous. These abnormal cells cannot fight off infection, and they interfere with the functions of other organs.
Successful treatment for leukemia depends on getting rid of all the abnormal leukocytes in the patient, allowing healthy ones to grow in their place. One way to do this is through chemotherapy, which uses potent drugs to target and kill the abnormal cells. When chemotherapy alone can't eliminate them all, physicians sometimes turn to bone marrow transplants.
In a bone marrow transplant, the patient's bone marrow stem cells are replaced with those from a healthy, matching donor. To do this, all of the patient's existing bone marrow and abnormal leukocytes are first killed using a combination of chemotherapy and radiation. Next, a sample of donor bone marrow containing healthy stem cells is introduced into the patient's bloodstream.
If the transplant is successful, the stem cells will migrate into the patient's bone marrow and begin producing new, healthy leukocytes to replace the abnormal cells.
Adult Stem Cell Transplant: Peripheral Blood Stem Cell Transplant
While most blood stem cells reside in the bone marrow, a small number are present in the bloodstream. These multipotent peripheral blood stem cells, or PBSCs, can be used just like bone marrow stem cells to treat leukemia, other cancers and various blood disorders. Since they can be obtained from drawn blood, PBSCs are easier to collect than bone marrow stem cells, which must be extracted from within bones. This makes PBSCs a less invasive treatment option than bone marrow stem cells. PBSCs are sparse in the bloodstream, however, so collecting enough to perform a transplant can pose a challenge.
Umbilical Cord Blood Stem Cell Transplant
Newborn infants no longer need their umbilical cords, so they have traditionally been discarded as a by-product of the birth process. In recent years, however, the multipotent-stem-cell-rich blood found in the umbilical cord has proven useful in treating the same types of health problems as those treated using bone marrow stem cells and PBSCs.
Umbilical cord blood stem cell transplants are less prone to rejection than either bone marrow or peripheral blood stem cells. This is probably because the cells have not yet developed the features that can be recognized and attacked by the recipient's immune system. Also, because umbilical cord blood lacks well-developed immune cells, there is less chance that the transplanted cells will attack the recipient's body, a problem called graft versus host disease.
Both the versatility and availability of umbilical cord blood stem cells makes them a potent resource for transplant therapies.
Stem Cell treatment for degenerative diseases
"Stem Cell treatment for degenerative diseases"
By Dr. Omar Gonzalez
Sister Nancy Boushey, Rio Grande City, TX , resigned to a life of pain with Rheumatoid Arthritis is healthy and normal today thanks to Dr Omar Gonzalez.
She hails him as a savior" my Good Shepherd, Jesus and His own good shepherd, Dr. Omar, have rescued me from a valley of darkness."
Cathy Zuker, Mt. Pleasant, MI, patient of multiple sclerosis for years was unable to walk unaided. She dragged her left leg and had to LIFT her legs manually when she got into the car. After her implants she can't stop smiling and the sparkle in her eye says it all" I have stopped taking one of two antidepressants without any negative effects. My friends say I 'glide'. I also wake up without a headache' "My mind and my life turned 360 degrees as my body became CANCER FREE!'" says an equally exultant Peggy Seagrist from Corpus Christi. She suffered from breast cancer, arthritis and a masticated tumor in the stomach. Multiple placenta implants and acupuncture brought her out smiling!
Dr. Omar Gonzalez' startling, mind-boggling inroads into biological regenerative medicine bring hope to millions in US and around the world , suffering from diseases like Alzheimer's, Multiple Sclerosis, Parkinson's, ALS, Epilepsy, Diabetes, Liver Disorders, Kidney Failure, Nervous System Disorders, Blood Disorders etc. Sci-fiction turns Sci-fact as Dr. Omar Gonzalez performs 'miracles' in 30 minutes to provide effective and economical biological solutions with stem cell transplantation therapy.
Sister Nancy Boushey had reservations regarding the source of placenta. Today, she recommends the procedure to millions with a smile as she realized that stem cells are from medically approved and safe adult placenta. The amniotic Membrane Stem Cell Implant developed by Dr. Omar Gonzalez is a unique concept to rebuild tissues and cells of degenerating organs. The amniotic epithelial stem cells from the amniotic membrane, a translucid sheet covering placenta are harvested and used to recreate and rebuild cells of practically any organ.
SCP-Stem Cell Panakea is a complete solution to the travails of all kinds of degenerative diseases which till now were considered incurable. 77 year old Lew Hollander got a new lease of life with two implants. He proclaims proudly "This year was my 18th Hawaii Ironman finish and I was the oldest finisher. This year finished in 15 hours and 46 minutes.One minute faster than in 1985,22 years earlier."
For biological solutions to hitherto incurable degenerative diseases and a peek into the wonders of SCP visit www.stemcellkp.com
By Dr. Omar Gonzalez
Sister Nancy Boushey, Rio Grande City, TX , resigned to a life of pain with Rheumatoid Arthritis is healthy and normal today thanks to Dr Omar Gonzalez.
She hails him as a savior" my Good Shepherd, Jesus and His own good shepherd, Dr. Omar, have rescued me from a valley of darkness."
Cathy Zuker, Mt. Pleasant, MI, patient of multiple sclerosis for years was unable to walk unaided. She dragged her left leg and had to LIFT her legs manually when she got into the car. After her implants she can't stop smiling and the sparkle in her eye says it all" I have stopped taking one of two antidepressants without any negative effects. My friends say I 'glide'. I also wake up without a headache' "My mind and my life turned 360 degrees as my body became CANCER FREE!'" says an equally exultant Peggy Seagrist from Corpus Christi. She suffered from breast cancer, arthritis and a masticated tumor in the stomach. Multiple placenta implants and acupuncture brought her out smiling!
Dr. Omar Gonzalez' startling, mind-boggling inroads into biological regenerative medicine bring hope to millions in US and around the world , suffering from diseases like Alzheimer's, Multiple Sclerosis, Parkinson's, ALS, Epilepsy, Diabetes, Liver Disorders, Kidney Failure, Nervous System Disorders, Blood Disorders etc. Sci-fiction turns Sci-fact as Dr. Omar Gonzalez performs 'miracles' in 30 minutes to provide effective and economical biological solutions with stem cell transplantation therapy.
Sister Nancy Boushey had reservations regarding the source of placenta. Today, she recommends the procedure to millions with a smile as she realized that stem cells are from medically approved and safe adult placenta. The amniotic Membrane Stem Cell Implant developed by Dr. Omar Gonzalez is a unique concept to rebuild tissues and cells of degenerating organs. The amniotic epithelial stem cells from the amniotic membrane, a translucid sheet covering placenta are harvested and used to recreate and rebuild cells of practically any organ.
SCP-Stem Cell Panakea is a complete solution to the travails of all kinds of degenerative diseases which till now were considered incurable. 77 year old Lew Hollander got a new lease of life with two implants. He proclaims proudly "This year was my 18th Hawaii Ironman finish and I was the oldest finisher. This year finished in 15 hours and 46 minutes.One minute faster than in 1985,22 years earlier."
For biological solutions to hitherto incurable degenerative diseases and a peek into the wonders of SCP visit www.stemcellkp.com
Managing diseases using stem cells
Cell based diseases such Parkinson’s, Alzheimer’s and diabetes were seen as the first candidates for being cured using stem cell transplantation. There is a probability that it would be possible one day. But some scientists are beginning to think that it will take another 15 years for a treatment using stem cells for Parkinson’s to emerge.
“The brain is so complex. We don’t understand every phenomenon in the brain,” said Colin McGuckin, Professor of Regenerative Medicine at the Newcastle Centre for Cord Blood, Newcastle, U.K. while explaining why it will take such a long time.
And unlike other organs, such as the heart, where the stem cells can be easily introduced, getting the stem cells into the brain poses an additional challenge.
Treating organs
According to Prof. McGuckin, treating organs and not cell-based diseases, may become a reality some time in the future. Even in the case of organs, such as the heart, the central idea is not about curing but managing the disease.
And if it were to come true, it would mark a paradigm shift in the way stem cells are seen as a treatment/cure option for many diseases.
The Newcastle centre has been in the forefront of cord blood stem cell research. The Centre was the first in the world to produce cord blood-derived embryonic stem cells, liver and pancreatic-like tissues, and neural cells from cord blood stem cells. It has a public cord blood bank started seven years ago and has about 1,000 samples.
Beta cell implant
Even in the case of diabetes, Prof. McGuckin feels that cord blood stem cells may only be able to treat diabetes. They may not be able to cure it.
The strategy is to implant beta cells that produce insulin anywhere near the blood system and allow these to control blood sugar. The strategy is the same for both Type 1 and Type 2 diabetes.
“The patient would get better [with the implant]. “Diet control is a must [even after the implant],” he stressed, “sensible diet is the best way to control diabetes. In both the cases, the implant is seen as a short term therapy.
The Newcastle centre is not looking at using cord blood stem cells for treating or curing diseases alone.
They have been using stem cells to produce human tissues to study the way certain diseases manifest and progress and look for possible ways of curing or treating them.
The team has already found that some genes expressed only at the embryonic stage, when growth is at its peak, reappear later in life. Ideally these genes should not be expressed after the foetal stage. But when they do appear, it results in cancerous growth.
Genes reactivated
“These genes are reactivated [at a later stage] by accident, Prof. McGuckin said. The Newcastle team found that some cancers of the skin, lung and prostate are caused this way. They have developed a family of drugs that can slow down such cancers.
“When we slow down cancer, we can use less of chemo and the chemo will have more time to act [on the cancer],” he said while explaining the advantages of slowing down cancer.
“Can’t cure cancer”
Apart from leukaemia, can stem cells be used to cure cancers? “Stem cells can’t cure cancer; they [stem cells] really don’t fight. The cancer cells would ignore stem cells as they don’t respect the environment,” said Prof. McGuckin emphatically. “We don’t promote stem cells for cancer [treatment].”
While some cancers are caused by faulty genes within the cells, some are switched on by other cells. Animal studies are currently underway to test the drugs that can address cancers caused by both, the faulty genes and by other cells.
Finding the causal factor, as in this case, is one of the uses of studying human tissues produced using stem cells. Using them for testing new molecules for treating diseases is another promising area.
When used prior to taking up animal trials, such human tissues can help reduce the number of animals used for testing. “Can’t [totally] replace animal testing overnight,” he stressed.
Multicentric trials
The team headed by Prof. McGuckin was in Chennai recently to explore the possibility of collaborating with institutions for undertaking joint multicentric global clinical trials using cord blood stem cells.
While using the patient’s bone marrow for treating his disease (autologous transplantation) is considered to be safe and numerous clinical trials are currently underway in India, Prof. McGuckin was critical of such trials.
“Even if it is an autologous [transplantation], we are taking the cells outside [the body] and there are chances of contamination. If it is a clinical trial, the researchers must work with other institutions abroad so that it is an international trial,” he underlined. “It is a risk if the trial is done in India [alone] and not internationally. Trials should be monitored.”
Source : R. PRASAD, THE HINDU
“The brain is so complex. We don’t understand every phenomenon in the brain,” said Colin McGuckin, Professor of Regenerative Medicine at the Newcastle Centre for Cord Blood, Newcastle, U.K. while explaining why it will take such a long time.
And unlike other organs, such as the heart, where the stem cells can be easily introduced, getting the stem cells into the brain poses an additional challenge.
Treating organs
According to Prof. McGuckin, treating organs and not cell-based diseases, may become a reality some time in the future. Even in the case of organs, such as the heart, the central idea is not about curing but managing the disease.
And if it were to come true, it would mark a paradigm shift in the way stem cells are seen as a treatment/cure option for many diseases.
The Newcastle centre has been in the forefront of cord blood stem cell research. The Centre was the first in the world to produce cord blood-derived embryonic stem cells, liver and pancreatic-like tissues, and neural cells from cord blood stem cells. It has a public cord blood bank started seven years ago and has about 1,000 samples.
Beta cell implant
Even in the case of diabetes, Prof. McGuckin feels that cord blood stem cells may only be able to treat diabetes. They may not be able to cure it.
The strategy is to implant beta cells that produce insulin anywhere near the blood system and allow these to control blood sugar. The strategy is the same for both Type 1 and Type 2 diabetes.
“The patient would get better [with the implant]. “Diet control is a must [even after the implant],” he stressed, “sensible diet is the best way to control diabetes. In both the cases, the implant is seen as a short term therapy.
The Newcastle centre is not looking at using cord blood stem cells for treating or curing diseases alone.
They have been using stem cells to produce human tissues to study the way certain diseases manifest and progress and look for possible ways of curing or treating them.
The team has already found that some genes expressed only at the embryonic stage, when growth is at its peak, reappear later in life. Ideally these genes should not be expressed after the foetal stage. But when they do appear, it results in cancerous growth.
Genes reactivated
“These genes are reactivated [at a later stage] by accident, Prof. McGuckin said. The Newcastle team found that some cancers of the skin, lung and prostate are caused this way. They have developed a family of drugs that can slow down such cancers.
“When we slow down cancer, we can use less of chemo and the chemo will have more time to act [on the cancer],” he said while explaining the advantages of slowing down cancer.
“Can’t cure cancer”
Apart from leukaemia, can stem cells be used to cure cancers? “Stem cells can’t cure cancer; they [stem cells] really don’t fight. The cancer cells would ignore stem cells as they don’t respect the environment,” said Prof. McGuckin emphatically. “We don’t promote stem cells for cancer [treatment].”
While some cancers are caused by faulty genes within the cells, some are switched on by other cells. Animal studies are currently underway to test the drugs that can address cancers caused by both, the faulty genes and by other cells.
Finding the causal factor, as in this case, is one of the uses of studying human tissues produced using stem cells. Using them for testing new molecules for treating diseases is another promising area.
When used prior to taking up animal trials, such human tissues can help reduce the number of animals used for testing. “Can’t [totally] replace animal testing overnight,” he stressed.
Multicentric trials
The team headed by Prof. McGuckin was in Chennai recently to explore the possibility of collaborating with institutions for undertaking joint multicentric global clinical trials using cord blood stem cells.
While using the patient’s bone marrow for treating his disease (autologous transplantation) is considered to be safe and numerous clinical trials are currently underway in India, Prof. McGuckin was critical of such trials.
“Even if it is an autologous [transplantation], we are taking the cells outside [the body] and there are chances of contamination. If it is a clinical trial, the researchers must work with other institutions abroad so that it is an international trial,” he underlined. “It is a risk if the trial is done in India [alone] and not internationally. Trials should be monitored.”
Source : R. PRASAD, THE HINDU
Sunday, March 2, 2008
Interview Extract of Indian Stem Cell Genius Dr.
Stem cell therapy is perhaps the brightest hope of modern medicine. Dr
S G A Rao, chairman and managing director of Bangalore-based Cryo Stem
Cell (Kar) Pvt Ltd, tells Harmony, "As there are no conventional cures
available for diseases caused because of cell death, stem cell-based
therapies will eventually become routine treatment."
Stem cells, the source of all blood cells, are able to regenerate
indefinitely, allowing them to form cells that replace those that fail
through disease, accident or old age. There are two types of stem
cells: adult, which include cells isolated from bone marrow; and
embryonic, which are isolated from a four or five-day old human
embryo. Although adult stem cells can replace worn-out cells and
repair tissues or organs, their scope is limited as they are
location-specific. Embryonic stem cells, on the other hand, are
undifferentiated and can develop into any adult cell. However, as
harvesting stem cells from embryos has caused a furore, especially in
Western, predominantly Christian nations, scientists have been
exploring other sources of stem cells-like blood from umbilical cord.
Such ethical opposition is rarely seen in India, a fact that has
enabled stem cell therapy to become available here. "I use stem cells
to treat conditions like paralysis, Parkinson's, Alzheimer's, motor
neurosis, cardiac complications, genetic disorders and spinal cord
damage," claims Dr Geeta Shroff (see interview), who runs Nu Tech
Mediworld Clinic in Delhi. "People who have not walked for 12 years
after spinal cord damage are now walking again." Costs, according to
her, are patient and disease-specific. "In cardiac cases, it takes Rs
20,000-Rs 30,000 a year, while for neurological cases, it costs about
Rs 3 lakh."
Shroff came into the public eye after she treated Congressman Ajit
Jogi in 2005. The 59-year-old former chief minister of Chattisgarh was
paralysed below the neck after an accident in 2004. After several
visits to Dr Shroff, he pronounced that he could sit without back
support, breathe normally and attain bladder control. Another patient
is Dr Vijaykumar Debsikdar, 45, who is undergoing treatment at Rs 1
lakh per year for an eight-year-old spinal cord injury that left him
paralysed in the right hand and from the waist down. "Now, I have
sensation in my legs," says the psychiatrist from Miraj, Maharashtra.
"I have started believing in God again."
It's one more testimonial for Dr Shroff. But some sections of the
global medical community have alleged that she has "failed to provide
evidence for scientific scrutiny". Even the Indian Council for Medical
Research has commented that the information submitted by Dr Shroff
lacked technical details. Meanwhile, the body has promised to set up
standard protocols for stem cell research in the country.
It's long overdue. As far back as 2002, Hyderabad-based LV Prasad Eye
Institute announced that it had pioneered the use of adult stem cells
in the treatment of human eye diseases. And companies such as Asia
Cryo Cell and Reliance Life Sciences have established cord blood stem
cell banks-here, you can bank stem cell from your baby's umbilical
cord to guard against future medical problems. Enrolment fees: Rs
60,000 to Rs 1 lakh.
INTERVIEW
"India can lead the world is stem cell therapy"
A specialist in fertility treatments like in-vitro fertilisation
(IVE), Dr Geeta Shroff branched into stem cell research in 2000. Her
clinic in Gautam Nagar, Delhi, offers embryonic stem-cell therapy,
along with other medical facilities. Though Shroff is unwilling to
divulge much about her techniques until her pending patient
application is granted, here's what she did tell Teena Baruah
Her work: I was introduced to stem cells in 1999 at a seminar in
Singapore. The idea of curing incurables excited me. I did research
for three years without any institutional backing so that I could work
on my terms. I create cell lines in my private IVF lab.
Ethic: I develop my stem cells from bio wastes so it doesn't bother
me. Being infertility specialists, we routinely get eggs and sperm to
create test-tube babies. Only one fertilised egg is introduced back to
the donor; the rest are discarded. We use them to create stem cell
lines after taking permission.
Safety: With my techniques, you don't get antigen-antibody reactions.
I have done over a hundred cases and I have seen no side effects like
tumours yet. Anyway, I follow the Indian Council of Medical Research's
draft guideline and treat only incurable cases.
Time line: Patients start feeling better within four to six weeks. But
the total process takes one or two years.
The possibilities: I can't grow back a complete organ yet; I need a
bigger lab and more funds for that. Right now, we are just replacing
dead tissue. Eventually, people over 60 could be going in for stem
cell shots to stay healthy. We could cure balding, grow new teeth, and
reserve degeneration in major body organs.
India ahead: Currently, the UK and US are caught up in moral debates
over stem cell therapy. According to British and American scientists,
it will take another five to 10 years to reach clinics. In India, I am
already doing it.
The criticism: A lot of people think I am faking it. And that's fine
by me. They have an image of a stem cell scientist and I don't fit
into that.
S G A Rao, chairman and managing director of Bangalore-based Cryo Stem
Cell (Kar) Pvt Ltd, tells Harmony, "As there are no conventional cures
available for diseases caused because of cell death, stem cell-based
therapies will eventually become routine treatment."
Stem cells, the source of all blood cells, are able to regenerate
indefinitely, allowing them to form cells that replace those that fail
through disease, accident or old age. There are two types of stem
cells: adult, which include cells isolated from bone marrow; and
embryonic, which are isolated from a four or five-day old human
embryo. Although adult stem cells can replace worn-out cells and
repair tissues or organs, their scope is limited as they are
location-specific. Embryonic stem cells, on the other hand, are
undifferentiated and can develop into any adult cell. However, as
harvesting stem cells from embryos has caused a furore, especially in
Western, predominantly Christian nations, scientists have been
exploring other sources of stem cells-like blood from umbilical cord.
Such ethical opposition is rarely seen in India, a fact that has
enabled stem cell therapy to become available here. "I use stem cells
to treat conditions like paralysis, Parkinson's, Alzheimer's, motor
neurosis, cardiac complications, genetic disorders and spinal cord
damage," claims Dr Geeta Shroff (see interview), who runs Nu Tech
Mediworld Clinic in Delhi. "People who have not walked for 12 years
after spinal cord damage are now walking again." Costs, according to
her, are patient and disease-specific. "In cardiac cases, it takes Rs
20,000-Rs 30,000 a year, while for neurological cases, it costs about
Rs 3 lakh."
Shroff came into the public eye after she treated Congressman Ajit
Jogi in 2005. The 59-year-old former chief minister of Chattisgarh was
paralysed below the neck after an accident in 2004. After several
visits to Dr Shroff, he pronounced that he could sit without back
support, breathe normally and attain bladder control. Another patient
is Dr Vijaykumar Debsikdar, 45, who is undergoing treatment at Rs 1
lakh per year for an eight-year-old spinal cord injury that left him
paralysed in the right hand and from the waist down. "Now, I have
sensation in my legs," says the psychiatrist from Miraj, Maharashtra.
"I have started believing in God again."
It's one more testimonial for Dr Shroff. But some sections of the
global medical community have alleged that she has "failed to provide
evidence for scientific scrutiny". Even the Indian Council for Medical
Research has commented that the information submitted by Dr Shroff
lacked technical details. Meanwhile, the body has promised to set up
standard protocols for stem cell research in the country.
It's long overdue. As far back as 2002, Hyderabad-based LV Prasad Eye
Institute announced that it had pioneered the use of adult stem cells
in the treatment of human eye diseases. And companies such as Asia
Cryo Cell and Reliance Life Sciences have established cord blood stem
cell banks-here, you can bank stem cell from your baby's umbilical
cord to guard against future medical problems. Enrolment fees: Rs
60,000 to Rs 1 lakh.
INTERVIEW
"India can lead the world is stem cell therapy"
A specialist in fertility treatments like in-vitro fertilisation
(IVE), Dr Geeta Shroff branched into stem cell research in 2000. Her
clinic in Gautam Nagar, Delhi, offers embryonic stem-cell therapy,
along with other medical facilities. Though Shroff is unwilling to
divulge much about her techniques until her pending patient
application is granted, here's what she did tell Teena Baruah
Her work: I was introduced to stem cells in 1999 at a seminar in
Singapore. The idea of curing incurables excited me. I did research
for three years without any institutional backing so that I could work
on my terms. I create cell lines in my private IVF lab.
Ethic: I develop my stem cells from bio wastes so it doesn't bother
me. Being infertility specialists, we routinely get eggs and sperm to
create test-tube babies. Only one fertilised egg is introduced back to
the donor; the rest are discarded. We use them to create stem cell
lines after taking permission.
Safety: With my techniques, you don't get antigen-antibody reactions.
I have done over a hundred cases and I have seen no side effects like
tumours yet. Anyway, I follow the Indian Council of Medical Research's
draft guideline and treat only incurable cases.
Time line: Patients start feeling better within four to six weeks. But
the total process takes one or two years.
The possibilities: I can't grow back a complete organ yet; I need a
bigger lab and more funds for that. Right now, we are just replacing
dead tissue. Eventually, people over 60 could be going in for stem
cell shots to stay healthy. We could cure balding, grow new teeth, and
reserve degeneration in major body organs.
India ahead: Currently, the UK and US are caught up in moral debates
over stem cell therapy. According to British and American scientists,
it will take another five to 10 years to reach clinics. In India, I am
already doing it.
The criticism: A lot of people think I am faking it. And that's fine
by me. They have an image of a stem cell scientist and I don't fit
into that.
Stem Cell India
It is perhaps not just about creating 'spare parts' for Human beings. Stem cell research has grown at a breathtaking pace that any philosopher worth his salt would not attempt to predict the Future. When ethical jingoism predominates the scenario in the west, it is interesting to note that many eastern countries have made rapid strides to reap maximum benefits out of this interesting science. India, already widely acclaimed as the IT [Information technology] superpower, is all set to exploit the benefits of BT [Bio Technology]. This article is an overview of the Stem Cell research in this part of the world.
A lost science?
In Adi parva, one of the chapters of Mahabharata, it is said that Kauravas were created from pinda [a ball of flesh], which Gandhari delivered after two years of pregnancy. It was then handed over to the sage Dwapayan, which was divided into one hundred parts and treated with herbs and ghee. The pieces were covered with cloth and kept in a chamber to cool for two years - out of which the Kauravas were born. "There cannot be any other explanation for this...." says Dr Matapurkar of the Delhi Maulana Azad Medical College.
The ancient sages of India must have perfected the art of regenerating entire human beings from cells. In fact Mahabharata clearly describes the various stages of processing pieces of flesh, which is in fact closely comparable to modern techniques of harvesting and processing embryonic stem cells [sans the sophistication!]. Perhaps stem cell research was altogether a lost science of ancient India.
A rediscovery?
Stem cell research in India made it to the headlines when the US Department of Health disclosed its interest in funding stem cell research in two Indian Centres - the Reliance Life Sciences [RLS] and the National Centre for Biological Sciences [NCBS].
The Reliance life Sciences [RLS]: backed by the industry major Reliance Ltd ranks third among the top-10 institutes world-wide working on stem cells, as stated by NIH and that came just when the RLS was 8 months old! Dr Firuza Parikh, the creator of the first ICSI [Intra Cytoplasmic Sperm Injection] child in India, heads the center.
The National Center for Biological Sciences had been working on stem cells for quite long [since 1999] and has three documented stem cell lines.
Another major institute involved in stem cell research in India is the L.V. Prasad Eye Institute, based at Hyderabad. The Institute caught the headlines recently when its doctors succeeded in transplanting a stem cell derived cornea to a patient who had lost his cornea - a treatment option available only in the US at the time.
The Maulana Azad Medical College, Delhi is yet another major institution involved in stem cell research. Studies here are led by Dr Balakrishna Matapurkar, one of the pioneers of stem cell research in India.
The Indian BT Boom
Recently the Ruby Hall Medical Research Centre, a subsidiary of Pune-based Ruby Hall Clinic, and Denmark-based biotechnology company Mesibo are soon to form a 49:51 joint venture with the aim to establish India's largest cord blood storage facility at Pune. This is apart from other major pharmaceutical companies in the country setting up their own stem cell and BT research centres all over the country.
These measures got a pat on the back when NIH announced its interest in funding research in stem cells in the country.
Ethics: the Indian Perspective
When ethical jingoism dominate the scenario in the west, eastern countries like India and Singapore are taking rapid strides to reap the benefits of this science to the maximum possible extent.
Unlike the public opinion in the west, which is against researches in this field, the public opinion in many eastern countries including India is far more supportive. The epics and innumerable religious texts that are in many parts of the world acclaimed as having scientific value, may partly be the reason for the scientific temper inculcated in this part of the world.
This openness is reflected in the Indian Department of Biotechnology [DBT]'s statement that India is open to stem cell research; and it promptly made regulatory provisions to control unethical practices, and in fact pioneered in bringing up a widely acceptable legal framework for research.
Conclusions
India has emerged as one of the major countries involved in Stem Cell research. A country which succeeded in becoming an IT superpower is also trying to replicate its success in BT. Apart from the pride and prestige earned by researchers in the country, the research in BT is adding more horsepower to the booming economy of the country. India, having an enviable combination of manpower and infrastructure is also involved in co-operations with other countries thus promoting the free flow of information gained through research and their utilisation in the betterment of Human lives.
A lost science?
In Adi parva, one of the chapters of Mahabharata, it is said that Kauravas were created from pinda [a ball of flesh], which Gandhari delivered after two years of pregnancy. It was then handed over to the sage Dwapayan, which was divided into one hundred parts and treated with herbs and ghee. The pieces were covered with cloth and kept in a chamber to cool for two years - out of which the Kauravas were born. "There cannot be any other explanation for this...." says Dr Matapurkar of the Delhi Maulana Azad Medical College.
The ancient sages of India must have perfected the art of regenerating entire human beings from cells. In fact Mahabharata clearly describes the various stages of processing pieces of flesh, which is in fact closely comparable to modern techniques of harvesting and processing embryonic stem cells [sans the sophistication!]. Perhaps stem cell research was altogether a lost science of ancient India.
A rediscovery?
Stem cell research in India made it to the headlines when the US Department of Health disclosed its interest in funding stem cell research in two Indian Centres - the Reliance Life Sciences [RLS] and the National Centre for Biological Sciences [NCBS].
The Reliance life Sciences [RLS]: backed by the industry major Reliance Ltd ranks third among the top-10 institutes world-wide working on stem cells, as stated by NIH and that came just when the RLS was 8 months old! Dr Firuza Parikh, the creator of the first ICSI [Intra Cytoplasmic Sperm Injection] child in India, heads the center.
The National Center for Biological Sciences had been working on stem cells for quite long [since 1999] and has three documented stem cell lines.
Another major institute involved in stem cell research in India is the L.V. Prasad Eye Institute, based at Hyderabad. The Institute caught the headlines recently when its doctors succeeded in transplanting a stem cell derived cornea to a patient who had lost his cornea - a treatment option available only in the US at the time.
The Maulana Azad Medical College, Delhi is yet another major institution involved in stem cell research. Studies here are led by Dr Balakrishna Matapurkar, one of the pioneers of stem cell research in India.
The Indian BT Boom
Recently the Ruby Hall Medical Research Centre, a subsidiary of Pune-based Ruby Hall Clinic, and Denmark-based biotechnology company Mesibo are soon to form a 49:51 joint venture with the aim to establish India's largest cord blood storage facility at Pune. This is apart from other major pharmaceutical companies in the country setting up their own stem cell and BT research centres all over the country.
These measures got a pat on the back when NIH announced its interest in funding research in stem cells in the country.
Ethics: the Indian Perspective
When ethical jingoism dominate the scenario in the west, eastern countries like India and Singapore are taking rapid strides to reap the benefits of this science to the maximum possible extent.
Unlike the public opinion in the west, which is against researches in this field, the public opinion in many eastern countries including India is far more supportive. The epics and innumerable religious texts that are in many parts of the world acclaimed as having scientific value, may partly be the reason for the scientific temper inculcated in this part of the world.
This openness is reflected in the Indian Department of Biotechnology [DBT]'s statement that India is open to stem cell research; and it promptly made regulatory provisions to control unethical practices, and in fact pioneered in bringing up a widely acceptable legal framework for research.
Conclusions
India has emerged as one of the major countries involved in Stem Cell research. A country which succeeded in becoming an IT superpower is also trying to replicate its success in BT. Apart from the pride and prestige earned by researchers in the country, the research in BT is adding more horsepower to the booming economy of the country. India, having an enviable combination of manpower and infrastructure is also involved in co-operations with other countries thus promoting the free flow of information gained through research and their utilisation in the betterment of Human lives.
Some More on Stem Cells
The classical definition of a stem cell requires that it possess two properties:
Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
Potency - the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent - to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells.
Potency definitions
Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.
Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.
Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. These cells can differentiate into embryonic and extraembryonic cell types.
Pluripotent stem cells are the descendants of totipotent cells and can differentiate into cells derived from any of the three germ layers.
Multipotent stem cells can produce only cells of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).
Unipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells).
Identifying Stem Cells
The practical definition of a stem cell is the functional definition - the ability to regenerate tissue over a lifetime. For example, the gold standard test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.
Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, where single cells are characterized by their ability to differentiate and self-renew.[4][5] As well, stem cells can be isolated based on a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells.
Embryonic stem cells
Main article: Embryonic stem cell
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos.[6] A blastocyst is an early stage embryo—approximately four to five days old in humans and consisting of 50–150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.
Nearly all research to date has taken place using mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia Inhibitory Factor (LIF).[7] Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic Fibroblast Growth Factor (bFGF or FGF-2).[8] Without optimal culture conditions or genetic manipulation,[9] embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the presence of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and SOX2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[10] The cell surface antigens most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[11]
After twenty years of research, there are no approved treatments or human trials using embryonic stem cells. ES cells, being totipotent cells, require specific signals for correct differentiation - if injected directly into the body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[12] Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.
Adult stem cells
Main article: Adult stem cell
Stem cell division and differentiation. A - stem cell; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation
The term adult stem cell refers to any cell which is found in a developed organism that has two properties: the ability to divide and create another cell like itself and also divide and create a cell more differentiated than itself. Also known as somatic (from Greek Σωματικóς, "of the body") stem cells and germline (giving rise to gametes) stem cells, they can be found in children, as well as adults.[13] Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood.[14] Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.).[15][16]
A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.[17] In mice, pluripotent stem cells are directly generated from adult fibroblast cultures.[18]
While embryonic stem cell potential remains untested, adult stem cell treatments have been used for many years to treat successfully leukemia and related bone/blood cancers through bone marrow transplants.[19] The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Consequently, more US government funding is being provided for adult stem cell research.[20]
Lineage
Main article: Stem cell line
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[21]
An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals dpp and adherins junctions that prevent germarium stem cells from differentiating.[22][23]
Main article: Induced Pluripotent Stem Cell
The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include several transcription factors including the oncogene c-Myc. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent.[24] However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy.
Treatments
Main article: Stem cell treatments
Medical researchers believe that stem cell therapy has the potential to dramatically change the treatment of human disease. A number of adult stem cell therapies already exist, particularly bone marrow transplants that are used to treat leukemia.[25] In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety of diseases including cancer, Parkinson's disease, spinal cord injuries, and muscle damage, amongst a number of other impairments and conditions.[26][27] However, there still exists a great deal of social and scientific uncertainty surrounding stem cell research, which could possibly be overcome through public debate and future research, and further education of the public.
Stem cells, however, are already used extensively in research, and some scientists do not see cell therapy as the first goal of the research, but see the investigation of stem cells as a goal worthy in itself.[28]
Controversy surrounding human embryonic stem cell research
Main article: Stem cell controversy
There exists a widespread controversy over human embryonic stem cell research that emanates from the techniques used in the creation and usage of stem cells. Human embryonic stem cell research is controversial because, with the present state of technology, starting a stem cell line requires the destruction of a human embryo and/or therapeutic cloning. However, recently, it has been shown in principle that embryonic stem cell lines can be generated using a single-cell biopsy similar to that used in preimplantation genetic diagnosis that may allow stem cell creation without embryonic destruction.[29] It is not the entire field of stem cell research, but the specific field of human embryonic stem cell research that is at the centre of an ethical debate.
Opponents of the research argue that embryonic stem cell technologies are a slippery slope to reproductive cloning and can fundamentally devalue human life. Those in the pro-life movement argue that a human embryo is a human life and is therefore entitled to protection.
Contrarily, supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It is also noted that excess embryos created for in vitro fertilisation could be donated with consent and used for the research.
The ensuing debate has prompted authorities around the world to seek regulatory frameworks and highlighted the fact that stem cell research represents a social and ethical challenge.
Key stem cell research events
1960s - Joseph Altman and Gopal Das present scientific evidence of adult neurogenesis, ongoing stem cell activity in the brain; their reports contradict Cajal's "no new neurons" dogma and are largely ignored.
1963 - McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow.
1968 - Bone marrow transplant between two siblings successfully treats SCID.
1978 - Haematopoietic stem cells are discovered in human cord blood.
1981 - Mouse embryonic stem cells are derived from the inner cell mass by scientists Martin Evans, Matthew Kaufman, and Gail R. Martin. Gail Martin is attributed for coining the term "Embryonic Stem Cell".
1992 - Neural stem cells are cultured in vitro as neurospheres.
1997 - Leukemia is shown to originate from a haematopoietic stem cell, the first direct evidence for cancer stem cells.
1998 - James Thomson and coworkers derive the first human embryonic stem cell line at the University of Wisconsin-Madison.
2000s - Several reports of adult stem cell plasticity are published.
2001 - Scientists at Advanced Cell Technology clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.[30]
2003 - Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth.[31]
2004-2005 - Korean researcher Hwang Woo-Suk claims to have created several human embryonic stem cell lines from unfertilised human oocytes. The lines were later shown to be fabricated.
2005 - Researchers at Kingston University in England claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical cord blood. The group claims these cells are able to differentiate into more types of tissue than adult stem cells.
August 2006 - Rat Induced pluripotent stem cells: the journal Cell publishes Kazutoshi Takahashi and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors".
October 2006 - Scientists in England create the first ever artificial liver cells using umbilical cord blood stem cells.[32][33]
January 2007 - Scientists at Wake Forest University led by Dr. Anthony Atala and Harvard University report discovery of a new type of stem cell in amniotic fluid.[5] This may potentially provide an alternative to embryonic stem cells for use in research and therapy.[34]
June 2007 - Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.[35] In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer[36]
October 2007 - Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.[37]
November 2007 - Human Induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors", and in Science by Junying Yu, et al., from the research group of James Thomson, "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells": pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of tumorigenesis due to c-myc and retroviral gene transfer remains to be determined.
January 2008 - Human embryonic stem cell lines were generated without destruction of the embryo[38]
January 2008 - Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts[39]
February 2008 - Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach: these iPS seem to be more similar to embryonic stem cells than the previous developed iPS and not tumorigenic, moreover genes that are required for iPS do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques
Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
Potency - the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent - to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells.
Potency definitions
Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.
Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.
Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. These cells can differentiate into embryonic and extraembryonic cell types.
Pluripotent stem cells are the descendants of totipotent cells and can differentiate into cells derived from any of the three germ layers.
Multipotent stem cells can produce only cells of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).
Unipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells).
Identifying Stem Cells
The practical definition of a stem cell is the functional definition - the ability to regenerate tissue over a lifetime. For example, the gold standard test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.
Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, where single cells are characterized by their ability to differentiate and self-renew.[4][5] As well, stem cells can be isolated based on a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells.
Embryonic stem cells
Main article: Embryonic stem cell
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos.[6] A blastocyst is an early stage embryo—approximately four to five days old in humans and consisting of 50–150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.
Nearly all research to date has taken place using mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia Inhibitory Factor (LIF).[7] Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic Fibroblast Growth Factor (bFGF or FGF-2).[8] Without optimal culture conditions or genetic manipulation,[9] embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the presence of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and SOX2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[10] The cell surface antigens most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[11]
After twenty years of research, there are no approved treatments or human trials using embryonic stem cells. ES cells, being totipotent cells, require specific signals for correct differentiation - if injected directly into the body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[12] Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.
Adult stem cells
Main article: Adult stem cell
Stem cell division and differentiation. A - stem cell; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation
The term adult stem cell refers to any cell which is found in a developed organism that has two properties: the ability to divide and create another cell like itself and also divide and create a cell more differentiated than itself. Also known as somatic (from Greek Σωματικóς, "of the body") stem cells and germline (giving rise to gametes) stem cells, they can be found in children, as well as adults.[13] Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood.[14] Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.).[15][16]
A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.[17] In mice, pluripotent stem cells are directly generated from adult fibroblast cultures.[18]
While embryonic stem cell potential remains untested, adult stem cell treatments have been used for many years to treat successfully leukemia and related bone/blood cancers through bone marrow transplants.[19] The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Consequently, more US government funding is being provided for adult stem cell research.[20]
Lineage
Main article: Stem cell line
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[21]
An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals dpp and adherins junctions that prevent germarium stem cells from differentiating.[22][23]
Main article: Induced Pluripotent Stem Cell
The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include several transcription factors including the oncogene c-Myc. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent.[24] However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy.
Treatments
Main article: Stem cell treatments
Medical researchers believe that stem cell therapy has the potential to dramatically change the treatment of human disease. A number of adult stem cell therapies already exist, particularly bone marrow transplants that are used to treat leukemia.[25] In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety of diseases including cancer, Parkinson's disease, spinal cord injuries, and muscle damage, amongst a number of other impairments and conditions.[26][27] However, there still exists a great deal of social and scientific uncertainty surrounding stem cell research, which could possibly be overcome through public debate and future research, and further education of the public.
Stem cells, however, are already used extensively in research, and some scientists do not see cell therapy as the first goal of the research, but see the investigation of stem cells as a goal worthy in itself.[28]
Controversy surrounding human embryonic stem cell research
Main article: Stem cell controversy
There exists a widespread controversy over human embryonic stem cell research that emanates from the techniques used in the creation and usage of stem cells. Human embryonic stem cell research is controversial because, with the present state of technology, starting a stem cell line requires the destruction of a human embryo and/or therapeutic cloning. However, recently, it has been shown in principle that embryonic stem cell lines can be generated using a single-cell biopsy similar to that used in preimplantation genetic diagnosis that may allow stem cell creation without embryonic destruction.[29] It is not the entire field of stem cell research, but the specific field of human embryonic stem cell research that is at the centre of an ethical debate.
Opponents of the research argue that embryonic stem cell technologies are a slippery slope to reproductive cloning and can fundamentally devalue human life. Those in the pro-life movement argue that a human embryo is a human life and is therefore entitled to protection.
Contrarily, supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It is also noted that excess embryos created for in vitro fertilisation could be donated with consent and used for the research.
The ensuing debate has prompted authorities around the world to seek regulatory frameworks and highlighted the fact that stem cell research represents a social and ethical challenge.
Key stem cell research events
1960s - Joseph Altman and Gopal Das present scientific evidence of adult neurogenesis, ongoing stem cell activity in the brain; their reports contradict Cajal's "no new neurons" dogma and are largely ignored.
1963 - McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow.
1968 - Bone marrow transplant between two siblings successfully treats SCID.
1978 - Haematopoietic stem cells are discovered in human cord blood.
1981 - Mouse embryonic stem cells are derived from the inner cell mass by scientists Martin Evans, Matthew Kaufman, and Gail R. Martin. Gail Martin is attributed for coining the term "Embryonic Stem Cell".
1992 - Neural stem cells are cultured in vitro as neurospheres.
1997 - Leukemia is shown to originate from a haematopoietic stem cell, the first direct evidence for cancer stem cells.
1998 - James Thomson and coworkers derive the first human embryonic stem cell line at the University of Wisconsin-Madison.
2000s - Several reports of adult stem cell plasticity are published.
2001 - Scientists at Advanced Cell Technology clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.[30]
2003 - Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth.[31]
2004-2005 - Korean researcher Hwang Woo-Suk claims to have created several human embryonic stem cell lines from unfertilised human oocytes. The lines were later shown to be fabricated.
2005 - Researchers at Kingston University in England claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical cord blood. The group claims these cells are able to differentiate into more types of tissue than adult stem cells.
August 2006 - Rat Induced pluripotent stem cells: the journal Cell publishes Kazutoshi Takahashi and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors".
October 2006 - Scientists in England create the first ever artificial liver cells using umbilical cord blood stem cells.[32][33]
January 2007 - Scientists at Wake Forest University led by Dr. Anthony Atala and Harvard University report discovery of a new type of stem cell in amniotic fluid.[5] This may potentially provide an alternative to embryonic stem cells for use in research and therapy.[34]
June 2007 - Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.[35] In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer[36]
October 2007 - Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.[37]
November 2007 - Human Induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors", and in Science by Junying Yu, et al., from the research group of James Thomson, "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells": pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of tumorigenesis due to c-myc and retroviral gene transfer remains to be determined.
January 2008 - Human embryonic stem cell lines were generated without destruction of the embryo[38]
January 2008 - Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts[39]
February 2008 - Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach: these iPS seem to be more similar to embryonic stem cells than the previous developed iPS and not tumorigenic, moreover genes that are required for iPS do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques
What are Stem Cells ?
Stem cells are cells found in all multi-cellular organisms. They retain the ability to renew themselves through mitotic cell division and can differentiate into a diverse range of specialized cell types. Research in the stem cell field grew out of findings by Canadian scientists Ernest A. McCulloch and James E. Till in the 1960s.[1][2] The two broad types of mammalian stem cells are: embryonic stem cells that are found in blastocysts, and adult stem cells that are found in adult tissues. In a developing embryo, stem cells can differentiate into all of the specialized embryonic tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of regenerative organs, such as blood, skin or intestinal tissues.
As stem cells can be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture, their use in medical therapies has been proposed. In particular, embryonic cell lines, autologous embryonic stem cells generated through therapeutic cloning, and highly plastic adult stem cells from the umbilical cord blood or bone marrow are touted as promising candidates.
As stem cells can be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture, their use in medical therapies has been proposed. In particular, embryonic cell lines, autologous embryonic stem cells generated through therapeutic cloning, and highly plastic adult stem cells from the umbilical cord blood or bone marrow are touted as promising candidates.
Saturday, January 12, 2008
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