Researchers at the Max Planck Institute for Molecular Biomedicine in Munster, Germany have simplified the method for generating iPS (induced pluripotent stem) cells from ordinary cells. Specifically, they have reduced the number of required reprogramming genes from four to one. The success of the new procedure, however, is heavily dependent upon the types of cells that are chosen to be reprogrammed.

Led by Dr. Hans Scholer, the team of scientists created iPS cells by reprogramming ordinary somatic (non-stem-cell) neural cells that were derived from aborted human fetal tissue. Clearly, the practicality of applying such a procedure to actual clinical therapies is quite low, due to the fact that brain biopsies are not easily obtainable from living subjects, and most countries have laws restricing the use of fetal and embryonic tissue. At least hypothetically, therefore, Dr. Scholer and his colleagues have proposed that neural cells derived from dental pulp might ultimately yield clinical applications.

Nevertheless, the choice of neural cells was critical to the success of the new procedure, since neural cells already express three of the four factors required for reprogramming into iPS cells, namely, Sox2, KLF4, and c-myc. Only the fourth factor, Oct4, is not naturally expressed and is therefore still required for administration to the cells. Although Oct4 was delivered via the conventional use of viral vectors, it was done without genetic integration, thereby yielding a final iPS cell which does not pose as many dangers and risks to potential patients as do those iPS cells that were reprogrammed from 4 genes.

The ultimate point of generating iPS cells is to create patient-specific stem cell lines which might then be utilized for the development of patient-specific therapies for the treatment of diseases that are unique to the individual patient. Of course, the creation of patient-specific stem cell lines has already been available with adult stem cells, and patient-specific therapies already exist from autologous (in which the donor and recipient are the same person) adult stem cells. Furthermore, with the "immune privileged", "universal donor" adult stem cells such as mesenchymal stem cells, patient-specific therapies are unnecessary since even allogeneic (in which the donor and recipient are not the same person) therapies have already been developed from adult stem cells. Adult stem cells, of course, are not nearly as "sexy" as embryonic stem cells nor even iPS cells, and therapies which already exist do not hold nearly the same irresistible fascination and "mystique" as do potential therapies which have not even been developed yet. Consequently, most of the media focus is on embryonic or iPS cells, not adult stem cells.

Last year, Dr. Scholer and his colleagues had succeeded in reducing the required number of reprogramming genes from 4 to 2. Prior to this latest achievement in which only one reprogramming gene is required, previous animal studies had indicated that the origin of the tissue plays an important role in determining differentiatability. In particular, cells derived from the stomach and the liver were found in mouse studies to be the most easily reprogrammable into iPS cells, but attaining stomach and liver biopsies from living human patients is also not always practical.

The 4 genes that have been conventionally used in the past to create iPS cells are precisely the same agents that render the iPS cells ineligible for clinical use, since the genes – one of which is an oncogene (which causes cancer) – introduce serious medical risks to the cells. Among other properties, the transcription factor Sox2 (sex-determining region Y) is essential for the undifferentiated self-renewal of embryonic stem cells, as is the protein and transcription factor Oct-4 (Octamer-4), a delicate balance of which is necessary for determining whether pluripotent cells differentiate or remain undifferentiated. A member of the Kruppel-like family of transcription factors, KLF4 is also simultaneously a gene and an antibody which plays a key role in cell proliferation and has been extensively studied for its role in cancer. Perhaps of greatest concern, however, is the proto-oncogene cMyc, mutations and overexpression of which have been implicated in many types of cancers. That fact that neural cells naturally express all of these factors except OCT4 is no doubt a topic of widespread research interest with applications in oncology and other fields beyond the immediate realm of neurology.

As Dr. Boris Greber, a member of Scholer’s team, explains, "Remarkably, it turns out that three of these four essential factors are already expressed in human neural stem cells, although not in skin cells, so we only needed to add one factor, OCT4. Ideally, we will be able to find a chemical that does the same job of expressing the factor without the need for a gene." Earlier this year, in fact, scientists in California announced the successful creation of iPS cells from mouse fibroblasts that were reprogrammed with a "cocktail" of proteins instead of the ordinary four genes, although this process is overall much less efficient. As Dr. Greber explains, "Without stable intervention using viruses, the frequency of reprogramming goes down and you have to wait a long time. We don’t have the perfect method yet." Nevertheless, as Dr. Greber further adds, in addition to being easier to reprogram, cells from neural tissue are also less prone to mutations than are cells from the skin.

Induced pluripotent stem (iPS) cells first burst into the news in 2006 when Dr. Shinya Yamanaka of Kyoto University in Japan announced the creation of these cells from ordinary mouse fibroblasts, which was succeeded the following year by the creation of iPS cells from human fibroblasts. Since then, the procedure has been reproduced numerous times by scientists around the world, a number of whom have contributed significant improvements to the process. Nevertheless, it is still not yet known whether or not these artifically produced cells will perform in vivo in a manner similar to that of naturally occuring cells. Since none of the iPS cells that have been created thus far are safe enough for clinical use, the actual therapeutic efficacy of these cells as a medical treatment remains unknown.

The U.S. adult stem cell veterinary company Vet-Stem announces a new service which offers customers an endless, indefinite supply of autologous adult stem cells.

The new service, known as "Vet-Stem Culture", is the latest innovation in a series of novel applications of Vet-Stem’s proprietary stem cell technology. Often in the news for their highly successful therapies for dogs and horses, Vet-Stem is the leading veterinary stem cell company in the U.S. and the first to commercialize a highly efficient and efficacious adult stem cell therapy for veterinary use. According to Vet-Stem’s highly popular procedure, veterinarians collect approximately 2 tablespoons of adipose (fat) tissue from their equine or canine patients, which is then shipped to Vet-Stem’s laboratories where adult stem cells are harvested from the tissue, processed, and returned within 48 hours to the vet who injects the stem cells directly into the animal at the site of injury. The therapy continues to garner increasing attention for its consistently high success rate in regenerating diseased and damaged bones, cartilage, ligaments and muscle. Additionally, pain medications are usually reduced or eliminated altogether in animals who receive the Vet-Stem treatment, and previously prescribed surgeries often become unnecessary after the therapy is administered.

Now, Vet-Stem’s new "Vet-Stem Culture" constitutes a method for re-culturing the same sample of adult stem cells indefinitely, thereby providing customers with an "everlasting" supply of stem cells, without the need to surgically collect more. Whenever a sample is sent to Vet-Stem for stem cell collection, the customer is given the option of having a small subsample stored for future culturing, should the need ever arise, for which a nominal annual fee which is charged which is less than the cost of additional surgical collection procedures.

As Vet-Stem founding CEO Dr. Robert Harman describes, "The Vet-Stem Culture service is a breakthrough in veterinary medicine, finally allowing pet owners to take preventative measures towards the future health of their pets. This option is going to eliminate the need for these injured and arthritic animals to go through multiple surgeries to extract stem cells. Even more, the results we see in animals treated with fat-derived stem cells are exceeding our expectations. Now they can continue to be treated naturally, with their own cells, to feel young over and over again."

This is not the first time that Vet-Stem has revolutionized veterinary medicine. From a July 2009 survey which Vet-Stem conducted, it was found that, of all the animals who received Vet-Stem’s autologous adult stem cell therapy, "62% of dogs with arthritis discontinued or decreased use of non steroidal anti-inflammatory drugs (NSAIDs)." Additionally, according to the results of the survey, "Further feedback from veterinarians and owners indicated that more than 75% of dogs with arthritis have improved quality of life after their treatment." Side effects from NSAIDS, especially gastrointestinal complications, remain a common and significant problem for animals, many of whom cannot tolerate NSAIDS precisely because of such adverse reactions. Vet-Stem’s autologous (in which the donor and recipient are the same animal) adult stem cell therapy has offered an excellent therapeutic alternative for such animals.

A regular feature on this website, Vet-Stem continues to pioneer new laboratory and clinical technology in the veterinary stem cell field, all of which has applications that are directly translatable to human medicine. No doubt it is just a matter of time before such technology is applied to the long-term culturing of human adult stem cells.

Veterinarians who wish to learn how to administer the adult stem cell therapy must first become certified by Vet-Stem, which also offers accredited RACE (Registry of Approved Continuing Education) classes.

In January of this year, to great fanfare and widespread publicity, the U.S. FDA (Food and Drug Administration) gave approval to the Geron Corporation for the commencement of clinical trials with human embryonic stem cells (hESCs). The trials, originally scheduled to begin this summer, were to be the first official U.S. government-approved clinical trials ever conducted with hESCs. On August 18, however, the FDA imposed a halt on the trials, even before the first patient could be enrolled.

Although Geron declined to offer a detailed comment at that time, representatives of the company have now finally issued a formal explanation. According to Geron officials, the FDA halt is the result of "non-proliferative cysts" that were found in preclinical animal studies.

Although the precise, scientific interpretation of "non-proliferative cysts" is highly debatable, nonscientists in the general public seem to be pacified by Geron’s extremely unscientific choice of words.

In actuality, this explanation contradicts initial reports in which Geron representatives attributed the FDA halt to "escalated dosage" that Geron scientists had reported in preclinical animal studies. (Please see the related news article on this website, entitled "Embryonic Stem Cell Trial Delayed", dated August 18, 2009, as originally reported in The New York Times). Now, however, "non-proliferative cysts" would seem to be a different explanation which is altogether entirely separate from "escalated dosage".

For those people with a modest understanding of scientific laboratory procedures, this latest statement by Geron does nothing to clarify matters at all, but, on the contrary, merely seems to obfuscate matters further. For the less scientifically inclined, however, any explanation at all would seem to be enough to restore full confidence and enthusiasm.

According to San Diego based WBB Securities analyst Stephen Brozak, "I think it provides people with a reasonable explanation. Everybody was afraid of the T-word, teratomas, and it clearly wasn’t that."

In fact, the results are not clear at all, and indeed, people have good reason to be cautious of "the T-word", since teratomas are, by definition, a required characteristic not only of embryonic stem cells but of all pluripotent stem cells in general. Since pluripotency is defined as the ability of a cell to differentiate into tissue from all 3 germ layers (the ectoderm, the mesoderm and the endoderm), the formation of a teratoma remains the universal laboratory standard by which embryonic and other pluripotent stem cells are identified. If a cell in the laboratory forms a teratoma, then it is, by formal definition, recognized to be a pluripotent stem cell – and this includes not only embryonic stem cells but also the more recently developed iPS (induced pluripotent stem) cells. Conversely, if a cell cannot form a teratoma in the laboratory, then it is recognized as not being pluripotent.

A very specific type of tumor, teratomas are known for their extremely hideous appearance since they often contain not only bones and organs but also hair and teeth. They appear, in fact, to be just like an embryo, though highly physiologically disorganized, as if all the bones and organs had been disassembled and randomly rearranged. Although teratomas are benign, in the sense that they do not metastasize, they can still pose a serious health hazard and can even be fatal if left untreated. A metastatic, malignant counterpart does exist, known as a teratocarcinoma, and in fact when early teratomas are first detected in the laboratory it is impossible to know at such a primitive stage whether the tumor is the benign or the malignant version. It is therefore a realistic possibility that pluripotent stem cells can cause the formation of malignant teratocarcinomas as well as the benign teratomas.

Since embryonic stem cells (ESCs) are required, by the formal definition of pluripotency, to cause the formation of teratomas, a major concern with medical therapies based upon ESCs is that such therapies should, logically and predictably, also form teratomas in the patients who receive such therapies. Indeed, exactly how, or if, one might be able to flip off the cellular and molecular "switches" that cause pluripotent cells to form teratomas remains a hotly debated point among stem cell scientists.

By sharp contrast, however, adult stem cells are not pluripotent and therefore are not capable of forming teratomas, unlike ESCs and iPS cells. Although such a lack of pluripotency was originally seen as a disadvantage of adult stem cells, it is now widely acknowledged to be a major advantage and one of the primary reasons why adult stem cells have already been in clinical use as clinical therapies, safely, for years, without even one teratoma ever being reported as a side effect.

Geron did not offer a detailed elaboration of the precise features of these "non-proliferative cysts" which were found to form in laboratory animals who received Geron’s novel, proprietary ESC therapy. Teratomas, of course, being nonmalignant, could also be described as "non-proliferative"; furthermore, teratomas are often routinely referred to as "cysts", especially within the medical community itself. It is not uncommon, for example, when teratomas form naturally on or around the ovaries, for a gynecologist to tell the patient that a "cyst" needs to be surgically removed, when in fact the "cyst" is a teratoma. Nevertheless, "cyst" is the more common, colloquial term that is more often used in casual discourse between doctor and patient.

It is not surprising, therefore, that many scientists remain skeptical about Geron’s claim that these "non-proliferative cysts" are not, in fact, the dreaded "T-word", teratomas. There are also many scientists who are wondering why it took Geron so long to issue a formal explanation, thereby apparently deliberately perpetuating the initial reports which cited "escalated dosage" as the reason for the FDA halt. Especially when the formal explanation that is now released to the press consists of such a simple, and simplistic, reason as the appearance of "non-proliferative cysts", many scientists are left wondering why it was exactly that Geron took so long to get around to releasing this explanation to the public.

Allowing separate, independent laboratories to analyze the cysts, and to check specifically for the differentiation of cells into all 3 germ layers, could settle the skepticism once and for all. It could also clarify the apparently erroneous perception, carelessly propagated throughout the public, that "escalated dosage" had something to do with the FDA’s reason for halting Geron’s clinical trial. Thus far, however, Geron has indicated no interest in allowing such a clarification.

Meanwhile, it would appear as though financial analysts are not necessarily scientists, and Stephen Brozak, among others, have now given Geron the new rating of a "strong buy" precisely as a result of Geron’s own description of "non-proliferative cysts". Consequently, shares of Geron’s stocks rose 25 cents, or 3.6%, to $7.18 at the close of trading today – up significantly after having fallen 10% as a result of the FDA halt that was announced on August 18.

According to Joseph Pantginis, an analyst at Merriman Curhan, "I believe that since the worst case scenario did not occur, investors are relieved." In fact, it is not at all known whether or not "the worst case scenario" did or did not occur. Until independent laboratories can check specifically for cells from all 3 germ layers, it cannot be known with any reliability or certainty whether or not these "non-proliferative cysts" are teratomas. Such a stance has nothing whatsoever to do with Geron in particular but rather it is a fundamental premise of the scientific method in general, which is founded upon repeatability and independent verification, without which, claims are meaningless – regardless of who makes such claims and regardless of whether the claims pertain to medical science or to the physics of planetary motion or to any other natural phenomenon.

Nevertheless, Pantginis was quick to add that Geron is not completely out of the woods just yet, as he points out that, "The potential timing of a release of the clinical hold is a complete black box and cannot be projected."

After all, the U.S. FDA actually employs scientists, some of whom might want to see further, independently verified evidence for the absence of cells from all 3 germ layers in these "non-proliferative cysts", before any proclamation about teratomas can be made.

Researchers at the University of Wisconsin at Madison are once again in the news headlines. This time, they have reprogrammed skin cells into retinal cells. The implications of such an accomplishment offer new hope to millions of people who suffer from vision problems.

Led by Drs. David Gamm and Jason Meyer, the team of researchers took ordinary fibroblasts and de-differentiated them into a more primitive state known as iPS (induced pluripotent stem) cells, a procedure which is becoming increasingly common in research laboratories throughout the world. The iPS cells, which resemble embryonic stem cells in their pluripotency, were then re-differentiated into retinal cells. Additionally, the scientists also compared the differentiation of iPS cells into retinal cells with the differentiation of embryonic stem cells into retinal cells, and both processes appeared to progress through the same stages over the same amount of time. Both types of cells developed first into neural cells, which then differentiated further into cells of the primitive eye field, which in turn differentiated further into the more specialized cells of the retina, which is the light-sensitive, image-forming membrane on the inside of the eye, without which vision is not possible. The final cells included retinal pigment epithelium cells as well as photoreceptor cells, both of which are commonly lost in diseases of the eye such as retinitis pigmentosa and age-related macular degeneration, the latter of which is estimated to afflict approximately 30 million people around the world, and which in the U.S. is the leading cause of blindness in people 55 years of age and older.

As Dr. Gamm explains, "If you understand and follow every stage of building a photoreceptor, you’re more confident because you’ve observed the assembly line. We can understand the disease better and see if there are ways to protect the cells or slow down the disorder." It is still not yet known, however, if these new retinal cells can actually function in vivo in the same manner as naturally occurring retinal cells. As Dr. Meyer adds, "That is among the next projects we’re working on."

First pioneered in 2007, simultaneously by Dr. James Thomson of the UW-Madison as well as by Dr. Shinya Yamanaka at Kyoto University in Japan, iPS cell technology is now considered to be one of the most promising fields in regenerative medicine. With the same pluripotency as embryonic stem cells, but without any of the ethical dilemmas and controversies, iPS cells seem to be able to do anything and everything that embryonic stem cells can do.

According to Dr. Robert Lanza, chief scientific officer at Advanced Cell Technology, who did not participate in the current study but has conducted similar research, "This is an important paper. It underscores the enormous potential of iPS cells, not only for treating diseases such as blindness, but as an important tool for understanding eye development. I think it will only be a matter of time before these iPS-derived cells are used in the clinic to help restore vision in patients."

Indeed, according to Dr. Gamm, who believes that clinical trials for retinal cell replacement could be conducted within the next 5 years, "That’s not pie in the sky anymore. I couldn’t have said that, even two years ago."

Shannon Miller, a 7-time Olympic Medalist and 9-time World Medalist, has signed a formal endorsement with StemCyte, one of the leading cord blood banks in the world. According to the terms of the agreement, Ms. Miller will be featured in a series of public awareness and advertising campaigns for the company.

In addition to her accomplishments as an Olympic gymnast, Ms. Miller is also a lawyer, having graduated in 2007 from Boston College Law School. She and her husband, John Falconetti, are expecting their first child in November of this year.

According to Ms. Miller, "As a former Olympic gold medalist, I’ve always sought out the best and healthiest decisions in life. As my husband and I have begun planning our family’s future, we have been thoroughly investigating the finest decisions for our baby. Cord blood banking was a no-brainer for us, and StemCyte was the obvious choice for where we wanted to store our baby’s cord blood."

In a statement made by Calvin Cole, vice president of operations in North America for StemCyte, "We were thrilled when Shannon approached StemCyte. We felt that as a world class athlete, expecting mom and role model for millions around the world, she was a perfect fit for StemCyte. As a decorated athlete who knows what it takes to be the best in the world, we’re thrilled that she clearly recognized StemCyte as the world’s best choice for parents and their cord blood banking decisions."

Headquartered in California and New Jersey, StemCyte also has facilities in India and Taiwan. As stated in their press release, StemCyte has supplied over 1,000 cord blood products for over 40 life-threatening diseases to over 200 leading worldwide transplant centers. StemCyte is also involved in the development of new umbilical cord-blood-based therapies, and is supporting the largest clinical study for the use of unrelated cord blood transplantation in the treatment of thalassemia, one of the most common genetic diseases in the world. Additionally, StemCyte is also supporting trials investigating regenerative spinal cord therapies. StemCyte has been contracted by the U.S. Department of HHS (Health and Human Services) to help establish a public National Cord Blood Inventory for unrelated transplant units.

South Korean prosecutors have told a Seoul court that Hwang Woo-suk should receive a four-year prison sentence for the scientific fraud that he committed in 2004 and 2005.

In addition to violation of bioethics laws, Hwang is also being charged with misappropriation of 2.8 billion won (approximately 2.25 million USD) in state funds. Although Hwang has apologized for his fraudulent reports, he has denied personal culpability, claiming that he was misled by junior researchers in his laboratory. Nevertheless, as one of the prosecutors explains, "The disappointment felt by the Korean people is enormous."

Formerly considered to be one of the world’s leading experts in the field of stem cell research, Hwang suffered a catastrophic fall from the prestige that he had previously enjoyed when he was found, in November of 2005, to have fraudulently reported the successful cloning of human embryonic stem cells. Specifically, he had authored two articles which were published in the highly respected journal Science in 2004 and 2005, and which initially catapulted Hwang into the international spotlight for his reports of the world’s first successful creation of human embryonic stem cells by cloning. The articles were later editorially retracted, however, when they were discovered to contain fabricated data, and Hwang quickly fell from fame to infamy. He subsequently confessed to charges of fraud, and was "indicted on embezzelment and bioethics law violations linked to faked stem cell research", according to media reports at the time. Additionally, he was expelled from the Seoul National University which had previously employed him, and the S. Korean government rescinded its financial support of his research and banned him from conducting further experiments on human cloning. To this day, the scandal has impacted S. Korean national law, which brought a formal halt to all experimentation on human cloning until this year. As Dr. Oh Il-hwan, a bioethics professor at the Catholic University Medical School in Korea, explains, "Hwang’s fall discouraged the government from supporting stem cell studies. It also meant that researchers in the field were the objects of scorn." Nevertheless, an investigational team at Seoul National University did verify that Hwang’s team had successfully produced the world’s first cloned dog, an Afghan hound named “Snuppy”.

Hwang is not without his supporters, who have staged high-profile, emotional rallies in the court, imploring a verdict that will allow Hwang a second chance. According to Lee Bong-gu, a lawyer for Hwang, "The prosecutors are trying to tear apart Hwang’s precious scientific evidence."

In 2006, with financial backing from his supporters, Hwang founded Sooam Biotech Research Foundation, which specializes in the cloning of animals and has produced several cloned dogs.

Hwang’s trial has been dragging on for three years and is predicted to continue into a fourth year, having been bogged down by technical testimony from numerous scientists who have testified about Hwang’s research. It is not known when a final verdict might be decreed.