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Program in Genes and Development, Center for Stem Cell and Development Biology, Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Tuesday, March 6, 2012
p53 Regulates Cell Cycle and MicroRNAs to Promote Differentiation of Human Embryonic Stem Cells
A Step-up Approach for Cell Therapy in Stroke: Translational Hurdles of Bone Marrow-Derived Stem Cells
Glover LE, Tajiri N, Weinbren NL, Ishikawa H, Shinozuka K, Kaneko Y, Watterson DM, Borlongan CV.
Abstract
Stroke remains a significant unmet condition in the USA and throughout the world. To date, only approximately 3% of the population suffering an ischemic stroke benefit from the thrombolytic drug tissue plasminogen activator, largely due to the drug's narrow therapeutic window. The last decade has witnessed extensive laboratory studies suggesting the therapeutic potential of cell-based therapy for stroke. Limited clinical trials ofcell therapy in stroke patients are currently being pursued. Bone marrow-derived stem cells are an attractive, novel transplantable cell source for stroke. There remain many unanswered questions in the laboratory before cell therapy can be optimized for transplantation in the clinical setting. Here, we discuss the various translational hurdles encountered in bringing cell therapy from the laboratory to the clinic, using stem celltherapeutics as an emerging paradigm for stroke as a guiding principle. In particular, we focus on the preclinical studies of cell transplantation in experimental stroke with emphasis on a better understanding of mechanisms of action in an effort to optimize efficacy and to build a safety profile for advancing cell therapy to the clinic. A forward looking strategy of combination therapy involving stem cell transplantation and pharmacologic treatment is also discussed.
Production of zebrafish offspring from cultured spermatogonial stem cells
Germ-line stem cells have the potential to be a very powerful tool for modifying the genetic information of individual animals. As a first step to use spermatogonial stem cells (SSCs) to enable genetic modification, we here describe effective long-term culture conditions for propagating zebrafish SSCs and for the production of offspring from these cultured SSCs after their differentiation into sperm in transplanted testicular cell aggregates. Dissociated testicular cells were cultured in specific medium with some modified supplements, including several mammalian growth factors. The spermatogonia actively proliferated and retained the expression of exogenous green fluorescent protein under the control of vas and sox17 promoters and also of promyelocytic leukemia zinc finger (Plzf), a marker of undifferentiated spermatogonia, after 1 month in culture. This is a longer period than the entire natural spermatogenic cycle (from SSCs to sperm). The use of subcutaneously grafted aggregates of these cultured spermatogonia and freshly dissociated testicular cells showed that these SSCs could undergo self-renewal and differentiation into sperm. Artificial insemination of these grafted aggregates successfully produced offspring. This culture method will facilitate the identification of new factors for the maintenance of SSCs and enable the future enrichment of genetically modified SSCs that will produce offspring in zebrafish.
What's all this about stem cells?
America is trialling it, Barack Obama is about to endorse it, Scottish doctors think it could cure a form of blindness, and a toddler is going all the way to China for it. Over the last month, it's been hard to miss all the news stories about stem cell therapy. We know that therapies based on stem cells are likely to be extremely beneficial to all sorts of disabled people in the future, but where are we with it all right now? I think it's time for a bit of a recap ...
What is stem cell therapy?
Stem cells are undifferentiated cells - lacking qualities that make them different or unique - which are capable of developing into any of the 200 different types of cell in the human body. They are derived from embryos, from the umbilical cord or, with greater difficulty, from the scarce stem cells in adults or children.
Stem cells can be used to grow tissues for transplantation - for example, heart muscle or brain cells or liver cells. They can also be used as models for disease, which can then be used in research - meaning better knowledge or less reliance on animal experimentation. This has recently been achieved for spinal muscular atrophy.
Stem cells can be used to grow tissues for transplantation - for example, heart muscle or brain cells or liver cells. They can also be used as models for disease, which can then be used in research - meaning better knowledge or less reliance on animal experimentation. This has recently been achieved for spinal muscular atrophy.
Who might be helped by these therapies?
People who have diseases or impairments which are caused by tissue damage or degeneration can potentially be helped by stem cell therapy. For example, people with diabetes, liver disease and Parkinson's, maybe even people with spinal cord injury.
A new trial is ex
A new trial is ex
Most of these therapies are only at the stage of initial trials in humans - for example, studies on corneal blindness and spinal cord injury are just starting.Does it work?Stem cell treatments have been successful in treating Severe Combined Immune Deficiency (SCID) a
nd a few other conditions in research settings. While stem cell therapy sounds good in theory, in practice it is very hard to grow specific cell types and control their growth safely. The children cured of SCID went on to contract a form of leukaemia. Research continues to understand why, and to improve safety and effectiveness.
When might therapies be available?
The first clinical trial of an embryonic stem cell therapy has just been authorised by the US Food and Drug Administration.
Clinical trials can take up to 10 years, so even if a therapy is shown to be successful, scientists or pharmaceutical companies then have to prove that it is safe. Animal trials have shown that therapies for spinal cord injury, muscular dystrophy and other conditions have great potential, but effective treatments are still a long way off. Therapies may be beneficial in the early days after a spinal cord injury, but not benefit those who have been injured for a long time.
Clinical trials can take up to 10 years, so even if a therapy is shown to be successful, scientists or pharmaceutical companies then have to prove that it is safe. Animal trials have shown that therapies for spinal cord injury, muscular dystrophy and other conditions have great potential, but effective treatments are still a long way off. Therapies may be beneficial in the early days after a spinal cord injury, but not benefit those who have been injured for a long time.
What's the ethical issue here?
Embryonic stem cell therapy depends on destroying embryos - usually surplus embryos from IVF treatment. Those who believe that life starts at conception will equate this to murder. The Vatican reaffirmed its opposition to embryonic stem cell research in December, but permits research using adult stem cells.
Another controversy is over somatic cell nuclear transfer, otherwise known as therapeutic cloning, which would enable stem cell tissues to be matched to the patient, but bring us closer to the possibility of reproductive cloning.
Under President Bush, creation of new embryonic stem cell lines was forbidden in America. President Obama is expected to permit a more liberal approach to research.
Another controversy is over somatic cell nuclear transfer, otherwise known as therapeutic cloning, which would enable stem cell tissues to be matched to the patient, but bring us closer to the possibility of reproductive cloning.
Under President Bush, creation of new embryonic stem cell lines was forbidden in America. President Obama is expected to permit a more liberal approach to research.
What's the political issue?
For those who take a pure social model approach to disability, the problem for disabled people is not their impairment but the barriers and discrimination within society. Stem cell therapy is offered as a cure for disability, whereas activists often deny their need or desire for cure.
Moreover, promises of scientific breakthroughs and wonderful medical treatments have been made for over fifty years, and there is scepticism about the current stem cell hyperbole. Superman actor Christopher Reeve was so convinced that stem cell therapy would cure spinal cord injury that he said that barrier removal and disability rights was unnecessary. Most others disagree.
Moreover, promises of scientific breakthroughs and wonderful medical treatments have been made for over fifty years, and there is scepticism about the current stem cell hyperbole. Superman actor Christopher Reeve was so convinced that stem cell therapy would cure spinal cord injury that he said that barrier removal and disability rights was unnecessary. Most others disagree.
So is it just a load of hype?
There is definitely lots of media excitement about stem cell therapy, as well as the occasional irresponsible announcement from a scientist. There are also big commercial interests involved: stories of miraculous stem cell treatments in less regulated countries such as China, Thailand, India and Russia are questionable, with vulnerable consumers being charged an average of 21,500 dollars for unproven therapies.
In Britain, many parents have been encouraged to pay for their infant's umbilical cord blood to be stored in private stem cell banks, with the hope that this might help with future disease. But scientists are sceptical as to whether the promised benefits will materialise.
But despite these negative stories, overall it is fair to say that leading scientists in the UK and US are responsible and very tightly regulated, and that many believe that ultimately this line of research will transform medicine.
You'll see many more news stories in the months and years ahead, so stay tuned for more updates on 'tailor made tissues'.
In Britain, many parents have been encouraged to pay for their infant's umbilical cord blood to be stored in private stem cell banks, with the hope that this might help with future disease. But scientists are sceptical as to whether the promised benefits will materialise.
But despite these negative stories, overall it is fair to say that leading scientists in the UK and US are responsible and very tightly regulated, and that many believe that ultimately this line of research will transform medicine.
You'll see many more news stories in the months and years ahead, so stay tuned for more updates on 'tailor made tissues'.
Chemical in bad breath 'influences' dental stem cells
Hydrogen sulphide, the gas famed for generating the stench in stink bombs, flatulence and bad breath, has been harnessed by stem cell researchers in Japan.
Their study, in the Journal of Breath Research, investigated using it to help convert stem cells from human teeth into liver cells.
The scientists claimed the gas increased the purity of the stem cells.
Small amounts of hydrogen sulphide are made by the body.
It is also produced by bacteria and is toxic in large quantities.
TherapyA group in China has already reported using the gas to enhance the survival of mesenchymal stem cells taken from the bone marrow of rats.
Researchers at the Nippon Dental University were investigating stem cells from dental pulp - the bit in the middle of the tooth.
They said using the gas increased the proportion of stem cells which were converted to liver cells when used alongside other chemicals. The idea is that liver cells produced from stem cells could be used to repair the organ if it was damaged.
Dr Ken Yaegaki, from Nippon Dental University in Japan, said: "High purity means there are less 'wrong cells' that are being differentiated to other tissues, or remaining as stem cells."
One of the concerns with dental pulp as a source of stem cells is the number that can be harvested.
However, the study did not say how many cells were actually produced.
Prof Chris Mason, a specialist in regenerative medicine at University College London, said: "It would be interesting to see how hydrogen sulphide works with other cells types."
Researchers find new pool of stem cells in heart
The researchers say the discovery may lay a foundation for much needed regenerative therapies aimed to enhance tissue repair in the heart. The damaged heart often doesn't repair itself well because of the incredibly hostile environment and wide-scale loss of cells, including stem cells, after a heart attack.
"In the end, we want to know how to preserve the stem cells that are there and to circumvent their loss," says Richard Harvey of the Victor Chang Cardiac Research Institute in
The newly described cardiac stem cells can be found in both developing and adult hearts, the evidence shows. As in the bone marrow and other organs, the colony-forming cells are found in the vicinity of blood vessels.
Harvey says despite the cells' ability to form those other cell types (a characteristic known as multipotency), he nevertheless suspects they have a bias toward heart tissue and their flexibility is a by-product of the need to remain responsive to the environment and to many types of injury.
While cell-based therapies do have potential for repairing damaged heart tissue,
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