A Step Toward Curing Parkinson's Disease and New Hope for Curing Many Other Degenerative Diseases of Ageing

Guardian
A research team at Sloan-Kettering have devised a range of methods for converting stem cells into specific differentiated cells. Their most recent triumph was the successful creation of dopamine producing cells from the substantia nigra -- the main part of the brain that degenerates in Parkinson's Disease.

Dr Studer and his colleagues, whose work is published in the journal Nature, found the specific chemical signals required to nudge stem cells into the right kind of dopamine-producing brain cells.

In a series of experiments, the team gave animals six injections of more than a million cells each, to parts of the brain affected by Parkinson's. The neurons survived, formed new connections and restored lost movement in mouse, rat and monkey models of the disease, with no sign of tumour development. The improvement in monkeys was crucial, as the rodent brains required fewer working neurons to overcome their symptoms. _Guardian

The finding brings researchers a step closer to testing a stem-cell-derived therapy in patients with this disorder. "We finally have a cell that seems to survive and function and a cell source that we can easily scale up," says Lorenz Studer, a researcher at the Sloan Kettering Institute and senior author on the new study. "That makes us optimistic that this could potentially be used in patients in the future."

The research also highlights the challenges of generating cells for tissue-replacement therapy, showing that subtle differences in the way the cells are made can have a huge impact on how well they work once implanted.

...While stem-cell researchers had previously been able to create dopamine-producing neurons from human stem cells, these cells did little to alleviate movement problems in animals engineered to mimic the symptoms of Parkinson's. In 2009, Studer and others developed a method of making the cells that more closely mimics the way they form during development. The resulting cells also carry more of the molecular markers that characterize dopamine-producing cells in the brain.

In the new research, published Sunday in the journal Nature, Studer's team found a way to make these cells even more efficiently. This is significant in terms of ultimately testing the therapy in humans; many methods for making specific types of cells are complex and yield small amounts of the desired product. _MIT TechnologyReview

This is a preliminary triumph for regenerative medicine, with every reason to expect that this development can move expeditiously from the animal lab into clinical research. The Sloan-Kettering team has made many improvements in the safe conversion of embryonic stem cells to mature differentiated cells, and have reduced the risk of tumour formation from these cells, when transplanted.

The ultimate goal is to be able to take donour cells from the patient himself, and turn those cells into young and vigorous cells of any cell type that is needed, in as large a number as needed -- even to the point of growing replacement organs from the person's own cells. Researchers are making progress in that area, but the pressing need to treat the growing number of ageing individuals with degenerative conditions may call for stop-gap measures such as the use of embryonic stem cell treatments described above.

Brian Wang has also looked at this story

Biosingularity Revolution Pushes Against Economic Collapse

Image via NextBigFuture
A revolution in regenerative medicine, genetic recombineering, synthetic biology, systems biology, and several other points of the biosingularity are pushing ahead despite three years of global economic downturn and counting, since the fall of 2008.

Brian Wang introduces us to the "accelerated evolution machine," pictured above.

Say hello to the evolution machine. It can achieve in days what takes genetic engineers years. So far it is just a prototype, but if its proponents are to be believed, future versions could revolutionise biology, allowing us to evolve new organisms or rewrite whole genomes with ease. It might even transform humanity itself.

...Because biological systems are so complex, it is a huge advantage to be able to tweak lots of genes simultaneously, rather than one at a time, she says. "In almost every case you'll get a different solution that's a better solution."

...By automating selection and using a few tricks, though, it should be practical to screen for far more subtle characteristics. For instance, biosensors that light up when a particular substance is produced could be built into the starting strain. "The power going forward will have to do with clever selections and screens," says Church.

As revolutionary as this approach is, Church thinks MAGE's most far-reaching potential lies elsewhere. He reckons it will be possible to use the evolution machine to make many thousands of specific changes to a cell's DNA: essentially, to rewrite genomes.

At the moment, making extensive changes to even the smallest genome is extremely costly and laborious. Last year, the biologist and entrepreneur Craig Venter announced that his team had replaced a bacterium's genome with a custom-written one (Science, vol 329, p 52). His team synthesised small pieces of DNA with a specific sequence, and then joined them together to create an entire genome. It was an awesome achievement, but it took 400 person-years of labour and cost around $40 million.

MAGE can do the same job far more cheaply and efficiently by rewriting existing genomes, Church thinks. The idea is that instead of putting DNA strands into the machine with a range of different mutations, you add only DNA with the specific changes you want. Even if you are trying to change hundreds or thousands of genes at once, after a few cycles in the machine, a good proportion of the cells should have all the desired changes. This can be checked by sequencing.

...As the technology improves and becomes routine, says Church, it could also be used to alter the cells used for cell-based therapies. Tissue-engineered livers grown from stem cells, say, could have their genetic code altered so that they would be immune to liver-destroying viruses such as hepatitis C. _NewScientist_via_NBF

The "evolution machine" has its work cut out for it, but it may very well speed up some projects which do not depend upon significant transformations of the genome. More sizeable genomic transforms are not likely to be possible using such a simplist approach. But future generations of such machines are likely to grow sophisticated enough to make the work of future Craig Venters much faster and simpler.
Researchers at the LA Children's Hospital built a fully functioning artificial small intestine in mice.

A man from Eritrea was recently given an artificial trachea transplant in Sweden. The trachea was grown on a scaffold inside a bioreactor.

Scientists have isolated the human blood cell progenitor stem cell, which is capable of growing all the various cellular components of the blood system.

Johns Hopkins researchers have identified a "super neural precursor stem cell" which can not only differentiate into specialised brain cells, but can also reproduce itself!

A partial list of companies involved in regenerative medicine research and development

The US has been the world's driver of scientific and biomedical R&D for several decades now. There has been some question as to how long American research could maintain its drive, if the nation's economy was dragged down by dysfunctional governmental economic and regulatory policies. Yet, despite the current US government's apparent war against the private sector, some areas of private R&D are still thriving -- although not as well as prior to the fall of 2008.

It is vital that private sector financing be central to advanced R&D, to prevent the type of politicisation of science which has frozen climatology in an infantile state of biased activism (via GWPF), rather than dispassionate observation and honest hypothesis testing.

Federal domination of science funding has two quite intended consequences: both individual scientists and major universities have become wards of Washington. For decades, academic sociologists have noted that almost all faculty party affiliations are with the Democrats. This is no conspiracy–it is merely like-minded individuals hiring other like minds and voting their best interest. _Forbes

New RiPS Stem Cells May Become Therapeutic Breakthrough

Scientists have invented an efficient way to produce apparently safe alternatives to human embryonic stem cells without destroying embryos, a long-sought step toward bypassing the moral morass surrounding one of the most promising fields in medicine.

A team of researchers at the Harvard Stem Cell Institute in Boston published a series of experiments Thursday showing that synthetic biological signals can quickly reprogram ordinary skin cells into entities that appear virtually identical to embryonic stem cells. Moreover, the same strategy can then turn those cells into ones that could be used for transplants.

"This is going to be very exciting to the research community," said Derrick J. Rossi of the Children's Hospital Boston, who led the research published in the journal Cell Stem Cell. "We now have an experimental paradigm for generating patient-specific cells highly efficiently and safely and also taking those cells to clinically useful cell types."

Scientists hope stem cells will lead to cures for diabetes, Alzheimer's disease, spinal cord injuries, heart attacks and many other ailments because they can turn into almost any tissue in the body, potentially providing an invaluable source of cells to replace those damaged by disease or injury. But the cells can be obtained only by destroying days-old embryos. _WaPo

A new induced stem cell technique from Harvard scientists promises to snowball into a bona fide breakthrough in regenerative medicine. Using messenger RNA (mRNA), a Harvard team has developed a safe and efficient technique for transforming virtually any cell type into an induced pluripotent stem cell.

Rossi said it was a happy coincidence that using RNA instead of changing the DNA was as much as 100-fold more efficient. He said the effect was possibly because the process more closely reflects how cells themselves transform.

Rossi successfully differentiated his stem cells into muscle cells using RNA, a process that may offer promise in gene therapy and other treatments. His method does not alter the cell's underlying genome, though Rossi admits that he does not yet understand what it does to the cell's epigenome, which controls expression of genes.

Rossi said that his cells, which he's named RiPS, for "RNA induced Pluripotent Stem" cells, are more like embryonic stem cells than traditional iPS cells because they have not been genetically altered.

Melton said the Harvard Stem Cell Institute, which includes several hundred stem-cell researchers from across Harvard University and its affiliated hospitals, will now be making its standard iPS cells with Rossi's method. _TechnologyReview

See WaPo RiPS video

Neuronal Pedophilia for Neurodegenerative Conditions

The old seem to imbibe an elixir of life by associating with younger ones of their kind. Swedish researchers have discovered that transplanted stem cells can rejuvenate degenerative neurons, litterally injecting new life into them.

The new report, co-authored by several international research groups and led by Karolinska Institutet, shows that stem cells transplanted into damaged or threatened nerve tissue quickly establish direct channels, called gap junctions, to the nerve cells. Stem cells actively bring diseased neurons back from the brink via cross-talk through gap junctions, the connections between cells that allow molecular signals to pass back and forth. The study found that the nerve cells were prevented from dying only when these gap junctions were formed. The results were obtained from mice and human stem cells in cultivated brain tissue, and from a series of rodent models for human neurodegenerative diseases and acute brain injuries.

"Many different molecules can be transported through gap junctions," says Eric Herlenius, who led the study. "This means that a new door to the possible future treatment of neuronal damage has been opened, both figuratively and literally."

The international team of scientist, beside Karolinska Institutet, included researchers from Sanford-Burnham Medical Research Institute, Harvard Medical School and Université Libre de Bruxelles.

Their report is published in the Proceedings of the National Academy of Sciences _SD

Stem cells may derive either from embryos or from more mature cells. With improvement in techniques for switching on and off expression of various genes will come the ability to create specific stem cells and tissues from a wide variety of mature cells originating within the patient's own body.

Growth factors produced by stem cells tend to regenerate older cells. Studies involving the use of growth hormones and growth factors directly to rejuvenate aging tissues and organisms tend to support the thesis. Using stem cells as "growth factor factories" obviates the need for repeated injections of hormone or factor. Here is a way to make "old stem cells" work like young stem cells again.

It is an analogous phenomenon to older men or women seeking out younger women (or men) for amorous association -- younger women (or men) disseminate pheromones into the local environment which tend to excite various passions -- including, but not limited to, the sexual ones.

When Gandhi routinely slept (chastely) with two underage girls, no doubt he experienced the benefits of "vital transference" at the same time he was strengthening his ability to resist temptation.

Stem Cells Restore Lost Cognitive Powers in Rats

Irradiated rats experience a 50% drop in cognitive function. But if the irradiated rats are transplanted with embryonic stem cells, they regain normal cognitive function within 4 months after radiation.

Radiotherapy for brain tumors is limited by how well the surrounding tissue tolerates the treatment. In receiving radiation at levels needed to treat tumors, patients suffer varying degrees of learning and memory impairment that can affect their quality of life.

"It's a progressive, debilitating side effect of cranial irradiation," Limoli said. "Any treatments showing promise at reversing this are worthy of pursuit."

In the UCI study, stem cells were transplanted into the heads of rats that had undergone radiation treatment. They migrated to a brain region known to support the growth of neurons, scientists observed, and developed into new brain cells.

Work is under way to determine how the transplanted stem cells improved cognition: Did they integrate into healthy tissue or did they help repair and support existing brain cells? _SD

The embryonic stem cells (ESCs) used for the UC Irvine study were derived from human embryos. They used basically the same ESC transplant technique for restoring brain function as they used to restore limb function in rats with transected cervical spines. Apparently the rats did not mind receiving ESCs from a different species.

Hopeful Stem Cell News Stories

Any adult cell can become a stem cell. This is a striking finding from the Cambridge, Mass. researchers.

“Essentially, all cells have the potential to become pluripotent. It is something that seems to happen to the cells under these conditions stochastically — that is, in a continuous, but probabilistic fashion,” Jaenisch explains. _Softpedia

Stem cell treatment restores limb function in rats with cervical spine injuries. The UCI team used human embryonic stem cells (pre-oligodendrocytes) that "rebuilt myelin, stopped tissue death and triggered nerve fiber regrowth".

Patients with advanced leukemia successfully treated with stem cells. Of the 58 patients, 35% survived 3 years -- an exceptionally good result for patients at such an advanced stage.

New technique developed to separate "safe" from "unsafe" stem cells before therapy. Stem cells vary in their likelihood to grow out of control and cause malignancies. "Undifferentiated" stem cells are more likely to lose control of growth.

Scientists from Invitrogen and the Buck Institute for Age Research, located in Novato, California, collaborated in developing this innovative solution that depletes greater than 99% of undifferentiated human embryonic stem cells from differentiated populations. They are presenting data on this new technology at the International Society for Cellular Therapy Meeting in San Diego. __LabmateOnline

Stem cells provide the bricks and mortar for constructing human tissues and organs. We are just beginning to learn how to create them, and to use them safely and efficaciously. In ten years -- if the US biomedical system has not been completely destroyed by government intervention -- we will look back to the present, amazed that human medicine was ever so primitive and hopelessly ineffective.

Cross-posted at Al Fin Longevity

New One-Step Reprogramming to Pluripotent Stem Cells

Scientists at UCSD and Salk have discovered a quicker and safer way to turn mature human cells into pluripotent stem cells. The new method only requires a single factor, and avoids the risky and expensive use of viral vectors and complicated gene insertions.

"Working with neural stem cells, we discovered that a single factor can be used to re-program a human cell into a pluripotent state, one with the ability to differentiate into any type of cell in the body" said Muotri. Traditionally, a combination of four factors was used to create iPSCs, in a technology using viral vectors – viruses with the potential to affect the transcriptional profile of cells, sometimes inducing cell death or tumors.

...By creating iPSCs from human neural stem cells without the use of viruses, the scientists learned something new. While the genetic transcriptional profile of the new iPSCs was closer to that of embryonic stem cells than to human neural stem cells, the iPSCs still carried a transcriptional "signature" of the original neural cell.

"While most of the original genetic memory was erased when the cells were reprogrammed, some were retained," said Muotri. He added that, in the past, it wasn't known if this was caused by the use of viral vectors. "By using a footprint-free methodology, we have shown a safe way to generate human iPSCs for clinical purposes and basic research. We've also raised an interesting question about what, if any, effect the 'memory retention' of these cells might have."

...The study, led by UCSD Stem Cell Program researcher Alysson R. Muotri, assistant professor in the Departments of Pediatrics at UCSD and Rady Children's Hospital and UCSD's Department of Cellular and Molecular Medicine, will be published online in PLoS ONE on September 17. _SD_via_MachinesLikeUs

While it is currently necessary to study both adult and embryonic stem cells, eventually the safe use of induced pluripotent stem cells from the patient's own body will supplant most therapeutic uses of embryonic cells.

Fat Americans Declared National Resource

"We've identified a great natural resource," said Stanford surgery professor and co-author of the research, Michael Longaker, MD, who has called the readily available liposuction leftovers "liquid gold." _SD _ ImpactLab

Liposuction leftovers can be turned into induced pluripotent stem cells (iPS cells), which function remarkably like embryonic stem cells (ESCs).

Nestled within this unwanted latticework of fat cells and collagen are multipotent cells called adipose, or fat, stem cells. Unlike highly specialized skin-cell fibroblasts, these cells in the fat have a relatively wide portfolio of differentiation options—becoming fat, bone or muscle as needed. It's this pre-existing flexibility, the researchers believe, that gives these cell an edge over the skin cells. _SD

Now that we know how valuable liposuction leftovers can be, it may be time to re-think our approach to obesity and overeating. Stem cells are, after all, an important key to future medical advances. Anything that may restrict access to this vital resource needs to be vigorously opposed.

Stem Cell Renaissance? Behind the Hype . . . .

President Obama's long anticipated and much heralded signing of new federal guidelines for the financing of embryonic stem cell research will help US scientists learn more of the mysteries of embryonic cell differentiation and manipulation. But in reality, the effect of the new rules will be far less significant for the future of regenerative medicine than most gullible news consumers will ever know.

.....the president’s support of embryonic stem cell research comes at a time when many advances have been made with other sorts of stem cells. The Japanese biologist Shinya Yamanaka found in 2007 that adult cells could be reprogrammed to an embryonic state with surprising ease. This technology “may eventually eclipse the embryonic stem cell lines for therapeutic as well as diagnostics applications,” Dr. Kriegstein said. For researchers, reprogramming an adult cell can be much more convenient, and there have never been any restrictions on working with adult stem cells.

For therapy, far off as that is, treating patients with their own cells would avoid the problem of immune rejection.

Members of Congress and advocates for fighting diseases have long spoken of human embryonic stem cell research as if it were a sure avenue to quick cures for intractable afflictions. Scientists have not publicly objected to such high-flown hopes, which have helped fuel new sources of grant money like the $3 billion initiative in California for stem cell research.

In private, however, many researchers have projected much more modest goals for embryonic stem cells. Their chief interest is to derive embryonic stem cell lines from patients with specific diseases, and by tracking the cells in the test tube to develop basic knowledge about how the disease develops.

Despite an F.D.A.-approved safety test of embryonic stem cells in spinal cord injury that the Geron Corporation began in January, many scientists believe that putting stem-cell-derived tissues into patients lies a long way off. Embryonic stem cells have their drawbacks. They cause tumors, and the adult cells derived from them may be rejected by the patient’s immune system. Furthermore, whatever disease process caused the patients’ tissue cells to die is likely to kill introduced cells as well. All these problems may be solvable, but so far none have been solved.

Restrictions on embryonic stem cell research originated with Congress, which, each year since in 1996, has forbidden the use of federal financing for any experiment in which a human embryo is destroyed. This includes the derivation of human stem cell lines from surplus fertility clinic embryos, first achieved by Dr. James Thomson of the University of Wisconsin in 1998.

President Clinton contemplated but never implemented a policy that would have allowed N.I.H.-financed researchers to study human embryonic stem cells derived by others. Research was able to begin only in August 2001, when President Bush, seeking a different way around the Congressional restriction, said researchers could use any lines established before that date.

Critics said the distinction between the Clinton and Bush policies lacked moral significance, given that each was intended to get around the Congressional ban, based on a religious and moral argument. The proposed Clinton policy amounted to: “Stealing is wrong, but it’s O.K. to use stolen property if someone else stole it.” The Bush policy was: “Stealing is wrong, but it’s O.K. to use stolen property if it was stolen before Aug. 9, 2001.”

Mr. Obama has put the proposed Clinton policy into effect, but Congressional restrictions remain. Researchers are still forbidden to use federal financing to derive new human embryonic stem cell lines. They will, however, be allowed to do research on new stem cell lines grown in a privately financed lab. _NYT

More research on embryonic stem cells will help scientists understand the intricate mechanisms of cell development. The knowledge spinoffs from this research will stretch far beyond regenerative medicine (RM) to cancer treatments, life extension technologies other than RM, and a much deeper understanding of biological mechanisms in general.

But all of that would have occurred without that much celebrated penstroke yesterday. And it is undeniable that the flow of NIH funds to non-embryonic stem cell research has been a boon to technologies that are more immediately applicable to the everyday regenerative cell and tissue treatments of the future -- treatment using the patient's own cells.

Science under Obama is every bit as political as science under any other president -- and will probably only grow more political with time. Obama's promotion of carbon penalties (disguised as "cap and trade") are a politicised hyping of the pseudo science of catastrophic global warming from anthropogenic CO2. Obama's carbon hysteria-based political meddling in the energy industry is likely to make Americans far more miserable, leaving them with far less resources to deal with exigencies, than if he had done nothing at all.

So let's celebrate the abundant biological future that will eventually come to us via all the avenues of research being followed. And let us not fall for the hype surrounding the gilded age of Obamanation.

Autologous Stem Cells Hold Most Promise in MS

Medical scientists are learning how to use autologous stem cells -- a person's own stem cells -- to treat serious illnesses such as multiple sclerosis (MS). A recent study at Northwestern University demonstrates an ingenious approach to the use of autologous stem cells:

In clinical trials, a team of scientists led by Richard Burt of Northwestern University in Chicago essentially rebuilt the immune system of 21 adults – 11 women and 10 men – who had failed to respond to standard drug treatments.

First they removed defective white blood cells that, rather than protecting the body, attacks the fatty sheath, called myelin, that protects the nervous system.

The immune systems were then replenished with so-called haemopoeitic stem cells – extracted from the patient's bone marrow – capable of giving rise to any form of mature blood cell.

....After an average follow-up period of three years, 17 of the 21 patients improved by at least one point on a standard disability scale, and none had a final score lower than before the stem cell transplant. _Cosmos

The ability to not only stabilise, but to actually reverse symptoms of advanced MS using autologous cells, is encouraging. Autologous cell therapies are preferred over cell transplants from donors or ESCs, due to the virtual absence of immune system rejection. That is why the new methods of inducing pluripotent stem cells from adult cells such as skin cells, will almost certainly be the preferred method of future medical rejuvenative and regenerative cell and (grown) organ replacement therapies.

Lancet article

Everything Old is New Again

Old brains can start acting like young brains again, thanks to University of British Columbia researchers:

The research reveals that the loss of plasticity is due to the protein calpain actively blocking the protein cortactin, which is responsible for the sprouting of new connections. The researchers reduced calpain activity in animal models to unlock the sprouting potential of neurons and found that when calpain activity is reduced neural plasticity is enhanced.

“The maintenance of neuronal connections is an active process that requires constant repression of the formation of nerve sprouts by the protein calpain to avoid uncontrolled growth,” says Mingorance-Le Meur, who is also a member of the Brain Research Centre at UBC and VCH Research Institute. “But a consequence of this role is that calpain limits neural plasticity and the brain’s ability to repair itself. The next step is to find a way to enhance neural plasticity without interfering with the good connections that are already in place. The next step is to find a way to enhance neural plasticity without interfering with the good connections that are already in place.” _PO

Younger brains capable of learning rapidly could change a lot of things in the developed world, where populations are aging. Between 1% and 2% of populations in the developed world may be walking around with Alzheimer's, and the proportion will only grow unless we learn how to stop the inexorable senescence.

What about the rest of the body? How do we regenerate aging livers, kidneys, hearts, lungs, pancreases, lymphatics and blood vessels? We would probably start with stem cells. But we want our own stem cells -- stem cells that are compatible with our immune systems. Fortunately, science is unraveling the tangled knot of inducing pluripotent stem cells from adult cells:

A team led by Scripps Research Institute scientists has for the first time developed a technique for generating novel types of....human stem cells with characteristics similar to mouse embryonic stem cells, currently the predominant type of stem cells used for creating animal models of human diseases in research. The technique potentially provides scientists with new sources of stem cells to develop drugs and treatments for human diseases.

The study, which appears in the December 18 online version of Cell Stem Cell and the January 2009 print edition of the journal, provides proof of principle that alternative sources of stem cells can be created. _SD

The new technique apparently creates human induced pluripotent stem cells (hiPSCs) that are very close to hESCs in behaviour. This research suggests that before long, all of us will be able to bank our own hiPSCs as a type of "old age insurance" against the loss of function of virtually any tissue type.

The ability to grow entire new organs from hiPSCs has not been demonstrated, but it is only a matter of time and engineering. If hiPSCs behave like hESCs, all of the cell types to make any tissue or organ are there, potentially.

A lot more work is necessary before we can expect routine rejuvenation procedures from these breakthroughs. A lot of other breakthroughs will be necessary before the entire repertoire of rejuvenation techniques are available to significantly prolong the period of fulfilled and productive human lifespan.

Good news? Yes, but superficial good news. Underneath it all, humans are still generally stupid, unwise, ignorant, bigoted, easily led, fanatically violent creatures. The path to the next level does not involve superimposing all of the marvelous high tech accomplishments of western science and engineering onto the masses of humans. The transplant simply will not take, despite the best wishes of Kurzweil and friends.

More later.

A Curious Deconstruction of the Human Embryo

Deep in the bowels of Stanford University's embryonic research labs, human embryos are being deconstructed to create: human sperm and eggs! Researchers believe that by working backwards -- from the embryo to the germ cells, they can provide solutions to the problem of infertility for a growing number of women who wait until their 30s or later to have children.

Q. HOW FAR HAVE YOU GOTTEN IN THIS QUEST?

A. We’re about halfway there, though I’m not sure if we’ve completed the easy or hard half. In a dish, we’ve gotten stem cells to make meiotic germ cells, the cells that give rise to eggs and sperm. What we haven’t been able to do yet is to figure out which supplements should be fed to the cells to get them to become germ cells capable of making embryos. Optimistically, we are three to five years from being able to do that.

Q. IN SPEECHES, YOU SAY THAT STEM CELL RESEARCH SHOULD BE THOUGHT OF AS A WOMEN’S HEALTH ISSUE. WHY?

A. Because in my lab, we’re using stem cell research to look for ways to make fertility treatments safer and more rational.

Considering all the heartbreak and expense of infertility treatments, this sort of research is something I believe women have a big stake in defending. _NYT _ via _ Instapundit

There are many reasons to study embryonic stem cells (ESCs). Other scientists are attempting to use ESCs to cure Parkinson's Disease and other neurodegenerative diseases. Some are using ESCs to try to cure heart failure, paralysis, stroke damage, and other fatal and disabling medical problems of all ages.

Infertility is a growing problem among populations of modern nations, where women have many alternative choices besides marrying young and raising large broods of children. Large numbers of women get sidetracked by careers and other non-familial concerns, so that by the time their minds begin to focus on a family, their bodies have gotten tired of cycling their eggs and uterus for nothing. This can lead to extended, expensive and often futile attempts to conceive artificially. The heartbreak of middle age female infertility. Not the greatest tear-jerker, as far as global problems go, but serious enough for the individuals involved.

In terms of longer-term demographic change leading to huge global social changes, western infertility is quite serious indeed. Whether the Stanford research into reverse creation of germ cells will contribute meaningfully toward supporting the underlying western ideas of enlightenment which made Stanford and other great universities of higher learning possible in the first place, remains to be seen.

Humans Slide, Genes Abide

Humans are sliding along the arrow of time, borne atop a genetic flow unbroken since the origin of DNA life. The more we learn about DNA and genetics, the more powerful the genetic flow is seen to be. Even "junk DNA" is more powerful than we ever imagined.

This research also shows that these repeats are anything but "junk DNA," since they provide a great source of evolutionary variability and might hold the key to some of the important physical differences that distinguish humans from all other species. _SD

Yes, junk DNA may be largely responsible for the origin of new species--and the reason why humans are different from close relatives such as the chimp. Another important and often overlooked reason for significant differences between related species is "CNVs," copy number variants. The number of copies of a gene in a genome can determine its influence in the organisms development and function.

CNVs in humans and chimpanzees often occur in equivalent genomic locations: most lie in regions of the genomes, called segmental duplications, that are particularly 'fragile'. However, one in four of the 355 CNDs that the team found do not overlap with CNVs within either species - suggesting that they are variants that are 'fixed' in each species and might mark significant differences between human and chimpanzee genomes. _PO

One of the most important distinctions of humans from other animals, is the sophistication and power of human language, in creating human culture. The propagation of human culture around the globe and across time is dependent upon genetic influences on the human brain, evolved over time. Scientists are beginning to learn more about the genetics of human language.

Molecular techniques then revealed that these changes occurred around 200,000 years ago — at just the point at which modern humans were evolving. This has led to much speculation about whether FOXP2 is a “gene for speech” — particularly given that people with major mutations, like the KE family, have major language defects. _Times

A recent genetic discovery by British scientists helps to unravel the mystery of human language slightly. One more small piece of a very large puzzle.

Variants of the CNTNAP2 gene are associated with the disorder known as specific language impairment (SLI) -- the unexplained difficulty with language that can involve repetition of nonsense words, the researchers said.

The gene has also been implicated in autism and could represent a genetic link between the two disorders, the scientists said. _WP

Genetics research is also proving a powerful tool in the quest to vanquish cancer.

Using cells donated by a woman in her 50s who died of leukemia, the scientists sequenced all the DNA from her cancer cells and compared it to the DNA from her own normal, healthy skin cells. Then they zeroed in on 10 mutations that occurred only in the cancer cells, apparently spurring abnormal growth, preventing the cells from suppressing that growth and enabling them to fight off chemotherapy. _NYT

One more small piece. Most people are unaware that the remarkable amount of scientific and technological research being done in the US is only possible due to excess wealth generated by the US' market economy. As politicians look for new ways to strangle the ability of the US economy to create excess wealth, savvy individuals will take a more jaundiced look at government.

The remarkable advances in recent stem cell research would have not been possible if not for the incredible progress previously made in genetics biotech. Researchers in Japan recently grew human brain tissue in a laboratory, from embryonic stem cells. Prelude to Grobyc?

The tissues self-organised into four distinct zones very similar to the structure seen in human foetuses, and conducted neuro-activity such as transmitting electrical signals, the institute said.

...The team's previous studies showed stem cells differentiated into different cells but until now they had never organised into functioning tissues.

...The tissues could also serve as "a mini organ" for use in studying the cause of the Alzheimer's disease and developing vaccines, it said. _AFP

Whether utilised as regenerative therapy for replacement of damaged brain, as research tools for understanding the organisation of neuronal and brain tissues better, or as Grobyc-style bio-brains for mechanical machines, these results are just the tip of the iceberg.

Research without an underlying "organising principle" is too often wasted, with the data and potential knowledge overlooked for long periods of time. If research findings are folded into ongoing meta-research efforts, nothing will be lost. It may take decades to find the optimal use for any given research findings. But as long as bioinformatics and other advanced computational and information procession tools advance along with applied research, the larger potential of what science is doing now will be examined eventually, although it is presently beyond the comprehension of most policy makers, pundits, and specialised workers and thinkers.

Stem Cells from Testicles, Stem Cells from Microvessels

Scientists from Germany and the UK have modified adult stem cells grown from the testicles of humans into cells which appear to be almost identical to embryonic stem cells.

The new stem cells, known as human adult germline stem cells (GSCs), were grown by researchers in Germany and the U.K. by adding special growth factors to spermatogonial cells extracted from testes. Spermatogonial cells are stem cells in the adult testis that normally generate only one type of differentiated cell (sperm). But with the right growth factors, these spermatogonial cells can change to become pluripotent. They begin to produce proteins normally made by embryonic stem cells (ESCs) and acquire the ability to differentiate into many different cell types. _

This is an intriguing finding which will require confirmation and elaboration. If a man's testicles can produce stem cells easily modified to form germline stem cells (GSCs)--virtual ESCs--then most men with testicles would be able to grow his own replacement cells. The search is also on for a similar cell in women.

More recent good stem cell news: multipotent stem cells have been found on the walls of capillaries and microvessels.

The scientists, led by Bruno Péault, PhD, deputy director of the Stem Cell Research Center at Children's Hospital, identified cells known as pericytes that are multipotent, meaning they have broad developmental potential. Pericytes are found on the walls of small blood vessels such as capillaries and microvessels throughout the body and have the potential to be extracted and grown into many types of tissues, according to the study. _ScienceDaily

Those bits of stem cell news combined with improved methods of inducing pluripotent stem cells from adult cells, all paint a rosy picture of the future of stem cell therapies and regenerative medicine.

Shinya Yamanaka of Kyoto University reported a new method, described today in the journal Science, that uses a tiny ring structure called a plasmid to deliver genes into mouse cells and turn them into stem cells. The technique eliminates the need to use viruses, which can trigger cancer, to transform cells. _Bloomberg

The plasmid method of inducing pluripotent stem cells, when perfected for human cells, may well provide a safe way of generating pluripotent cells for those both with and without viable testicles.

The biotech revolution is just beginning. Combined with nanotech and advanced information science, the world of the very small is destined to grow very large.

Can Exercise Grow More Brain Cells?

Jack LaLanne will be 94 years old September 26. His life has been a tribute to the benefits of lifelong exercise. Science is slowly substantiating the essential truths behind LaLanne's long crusade.

Exercise is essential to building new muscle cells in a damaged heart, or in skeletal muscles. Exercise kicks stem cells into the circulation, where they can migrate to where they are needed.

Researchers at the University of Gothenberg have recently shown that exercise stimulates the growth of new brain cells from neural stem cells, aiding recovery from brain damage.

Researchers at the Sahlgrenska Academy in Gothenburg show for the first time that exercise helps restore stem cell growth and improves behavior in young mice that suffered damage to the brain induced by a clinically relevant dose of radiation.

The researchers believe that these results are also applicable to children that have suffered damage due to radiotherapy of brain tumors.....The results from the study demonstrated that irradiated mice showed increased motor activity and altered movement patterns that were normalized if they were allowed to exercise. In addition, the mouse brains contained 50% more stem cells than their non-exercising counterparts. _SD

Children are much better able to produce stem cells to replace damaged body tissue than are adults. But the capacity to regenerate damaged tissue never goes away completely. It is quite possible that individuals who exercise regularly throughout life, are maintaining their bodies and brains in a much higher state of function, due to continued stem cell rejuvenation.

The long-term ramifications of natural stem cell stimulation--exercise, sleep, diet, herbs, meditation, etc etc--remain to be studied.

Why Do Antidepressants Take 6 Weeks to Work?

Until fairly recently, psychiatrists and neuropharmacologists have been puzzled by the several-week delay in onset of antidepressant efficacy of commonly prescribed mood elevators. It shouldn't take that long to boost neurotransmitter levels. But straight from central casting, the neural stem cell made its appearance in the science annals, and it was found that some antidepressants stimulate the differentiation of neural stem cells to mature nerve cells. Voila! New neurons--a feat once thought impossible!--from neural stem cells, with a little help from pharmacology. Recent work from the University of Texas supports that hypothesis.

...Antidepressants act very quickly to increase levels of natural compounds, called neurotransmitters, which nerve cells use to communicate. It takes several weeks to several months, however, for the patients who respond to such treatments to feel less depressed. Dr. Parada said this implies that some other long-term mechanism is also at work.

...Matching the timeframe for medicated patients to feel less depressed, it takes several weeks for new nerve cells to grow, Dr. Parada said. This parallel effect, he said, may mean that antidepressants need to stimulate growth of new cells in the dentate gyrus in order to achieve their full effect. _Sciencedaily

Antidepressants stimulate the production of new nerve cells in the hippocampus, and appear to protect nerve cells from apoptosis, at least in animal studies. The time delay for the mood elevation from antidepressants appears to be caused by the time to differentiation and integration of new neurons.

All this time, psychiatrists have been engaging in regenerative neuromedicine, and did not even realise it. Now that we have a better idea of what we are doing, perhaps we can learn to do it better?

Brain Rejuvenation Using Intravenous Cord Blood

Image Source

Researchers in Florida have managed to rejuvenate the brains of aging mice with a single injection of human cord blood cells in a peripheral vein. The single cord blood cell injection resulted in new progenitor stem cells in the mouse hippocampus, and new nerve cell formation.

Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation.

We determined that human umbilical cord blood mononuclear cells (UCBMC) given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis.

The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain.

...Not only do the results of this study provide novel insight into the state of the aged stem cell niche, the ability of the UCBMC to exert their effects while being administered minimally invasively may make translation to the clinical setting more likely. For this reason it will be important in future studies to determine the most efficacious dose and dosing regimen. Nevertheless, this is the first time that a systemic injection of hematopoietic cells has been shown to restore the regenerative potential of the aged brain, providing a novel insight into how the regenerative potential of the aged stem cell niches could be restored.

...The effects of UCBMC have been attributed to changes in the microenvironment of the brain, through the release of trophic factors or by reducing inflammation, and not by a direct replacement of cells [21-23]. UCBMC contains a number of cell types including B-Cells and T-Cells, as well as, mesenchymal and endothelial progenitor cells. UCBMC is also a rich source of CD34⁺ hematopoietic stem cells [24-26]. It was recently demonstrated that a systemic injection of UCBMC cells could suppress inflammation in the brain following stroke. Moreover, the effects of UCBMC cells seemed to shift the cytokine expression from a Th1 response to a Th2 response [20,23,27]. In addition to the immune modulatory effects, UCBMC cells also produce a number of trophic factors including, but not limited to, VEGF, nerve growth factor, and cytokine colony stimulating factor-1, thrombopoietin, and IL11 [20,28,29]. ___BiomedCentral__via_madscience__via__TechnutNews

It is important to understand that the cells that were injected into the peripheral veins of mice were human umbilical cord blood mononuclear cells (HUCBMCs). The results are somewhat startling, given that the injected cells were not neural stem cells, the cells were not injected directly into the brain, and the cells were given in a single dose only. It will be important for the researchers to tease out the important cellular and trophic factors present in the UCBMC's that may have led to the rejuvenatory effects.

This is a line of research that I am interested in following further.

Adult Stem Cells vs. Embryonic Stem Cells? No Contest!

On the one hand, with adult stem cells, you have the potential to create stem cells from your own tissue. A lot of progress is being made--including the recent Harvard Medical School study that went all the way from skin biopsy to embryonic stem cell.

"Ours is the only group to go from skin biopsy to cell line," Daley said in a statement.

They said they are now working to generate the so-called induced pluripotent stem cell or iPS cells to match a variety of diseases.

Daley cautioned the approach is not ready to test in people. The researchers use viruses called retroviruses to carry in four genes that transform the skin calls back into their primitive and malleable state.

And when injected into mice, the human iPS cells often formed tumors. Daley's team is afraid this method might cause cancer or other unforeseen problems in human beings.

SciAm

So pluripotent adult stem cells (ASCs) are getting better--but are not ready for the clinic yet. What about embryonic stem cells? There is some progress on that front as well.

In a groundbreaking experiment scientists from International Stem Cell (ISC) Corp. derived four unique embryonic stem cell lines that open the door for the creation of therapeutic cells that will not provoke an immune reaction in large segments of the population. The stem cell lines are “HLA-homozygous,” meaning that they have a simple genetic profile in the critical areas of the DNA that code for immune rejection. The lines could serve to create a stem cell bank as a renewable source of transplantable cells for use in cell therapy to replace damaged tissues or to treat genetic and degenerative diseases.

Science Daily

Interesting. The International Stem Cell Corp. ESCs are made for specific tissue matching to the recipient--similar to how blood transfusions are matched. This would allow for large scale "stem cell banks" in every large medical center. Specific stem cell types could be matched to the recipient within hours for a minimal cost. These ISC Corp. line of ESCs are derived from parthenogenic embryos--unfertilised eggs.

If a person planned ahead, and created large numbers of their own pluripotent stem cells in advance, and carried them with them wherever they traveled in case of emergencies, one's own stem cells would obviously be preferable. But in an urgent or emergency situation, having standard lines of tissue-matchable standard cell line ESC's would be invaluable.

There is really no contest between the two approaches. Both are important.

"Understanding how to derive stem cells from embryos may teach us how to make the reprogramming process that much more efficient," Daley said.

It was by studying embryonic stem cells that researchers learned which genes are needed to make ordinary cells act in the same way. Daley's lab used four genes and discovered that two were essential for turning back the clock and making the skin cells act like embryo cells, and two others helped them grow efficiently.

His team also converted fetal and embryonic cells into various cell types, and found these were far easier to work with.

"The fact that embryonic and fetal cells convert more efficiently than adult cells was suggested in mouse studies but the pattern is quite apparent with human cells," Daley said. "This suggests that there are many aspects of the biology of reprogramming we still need to understand to make the process more efficient."

Sciam

Skin-Cell Stem-Cells Cure Sickle Cell Mice

An American team of scientists have cured mice of their sickle cell anemia using stem cells from skin cells--instead of cloned embryonic stem cells. This takes this no-clone stem cell approach yet one step closer to use on humans with genetic diseases and other conditions amenable to stem cell treatments.

A Japanese team made headlines worldwide a few days ago when it announced a way to turn adult skin cells, taken from a woman's face, into embryonic stem cells, the body's building blocks used during growth and repair, which offer a way to treat patients suffering a vast range of conditions with personalised replacement cells and tissue.

Now "direct reprogramming," which offers an alternative to the use of human eggs and cloning, has been used for the first time to cure a disease, marking the first "proof of principle" that this method has great promise in treating hereditary blood disorders, though the potential to rebuild a diseased or damaged body is much greater even than this.

Mice with the faulty gene responsible for human sickle-cell anaemia were treated successfully, so they made normal red blood cells instead of those of a sickle shape that clog blood vessels, causing severe pain, anaemia and, over time, a wide range of organ damage, even death.

More at Source

Much research needs to be done to ensure safety and efficacy of this technique for treating human diseases and/or trauma, but the early steps appear to lead in the right direction.

Stem Cell Lines For Sale--The Market Steps Up

The US President Bush has held firm in his opposition to federal financing of creation of most new embryonic stem cell lines. Without US government financing of new stem cell lines, the task has fallen upon other governments, private foundations, US state governments such as California, and now--private companies are offering new stem cell lines from discarded IVF embryos, for US $10,000.

You would expect this type of company to arise in the US, and particularly in California--where trends tend to begin.

A company in California called StemLifeLine has announced that it will offer a service to generate stem cells from excess frozen embryos stored after in vitro fertilization (IVF). The company promises a huge potential payoff: the cells could one day be used to treat disease in the buyers or in their families. But the service is already garnering criticism from some scientists and ethicists who say that without current medical uses for those cells, there's no point in people paying for them.

...The new service is meant to take advantage of a growing interest in the field of regenerative medicine. Stem cells from adult blood or umbilical-cord blood are already used to treat some diseases, including sickle-cell anemia and several forms of leukemia. But these cells are largely limited to treating blood-related disorders and can't be grown in large numbers. Embryonic stem cells, on the other hand, can be coaxed to form virtually any type of cell in the body and can theoretically be replicated indefinitely. Scientists are developing ways to use them to replenish cells lost or damaged in ailments such as diabetes, Parkinson's disease, and heart disease.

...Couples who have had children via IVF are often left with extra embryos--and the rather difficult decision of what to do with them. As of 2003, an estimated 400,000 embryos remained in cryopreservation in the United States. Embryos can be donated to research or to other couples, destroyed, or left languishing in frozen storage.

...The technology to derive these cells is not new. Scientists at StemLifeLine use a similar procedure to that employed by research scientists for almost a decade, although the StemLifeLine scientists have refined it so that the resulting cells are fit for human use. For less than $10,000 (actual price depends on the collaborating IVF clinic), clients can send in their excess embryos and, in return, receive a line of stem cells that have been "quality assured," meaning they have been checked for the molecular markers that signify that the cells can be differentiated into multiple cell types. The company received certification as a tissue bank from the state of California last month, and it's in the process of generating cell lines for its first group of clients.

Technology Review

It is good to see some entrepreneurial spirit emerging in stem cell/regenerative medicine. Since regenerative medicine will be one of the most important branches of medical science in the near future, it is refreshing to see that it will not fall completely under the thumb of the US federal government.

In a market economy, the government is not expected to finance every possible need or desire for the public. Most Americans have been rather slow to realize this, but it seems that some of them are slowly waking up. Financing of large new scientific ventures and exploratory areas of science has--since the days of FDR and the Manhattan Project--been ceded to the federal government, in the US. But the US government is operating in a budget deficit, which will only get worse as entitlement spending kicks in for the aging populace.

The US public has been lulled into expecting the federal government to do more and more for them over the decades. This expectation is killing their own self-reliance and enterprise. While the US has not sunk as deeply into this "total government reliance" as most European countries, and some other Anglospheric countries, the trend is clear and almost irrevocable.

The more thoroughly the government attempts to control financing and access to regenerative medicine, the more the grey and black markets will step in to provide the service that governments--with their conflicting goals and crumbling infrastructures--cannot or will not provide.

More background on stem cells here and here.