The biotech company BioLife Solutions announced today the launch of its new biopreservation media product platform, known as BloodStor 55-5. The new technology offers significant improvements to the field of adult stem cell cryopreservation, and is expected to drive an increase in revenue at cord blood banks.

Already recognized as a leading manufacturer, developer and marketer in the field of biopreservation tools, BioLife Solutions is focused on the commercialization of novel ways to bank cells, tissue and organs. BloodStor 55-5, it’s newest product, is packaged in standard, single-use sterile vials of various volumes and is formulated with 55% USP grade DMSO and 5% USP grade dextran-40 in water for injection quality (WFI) water. BloodStor 55-5 also supports a common cord blood processing protocol.

According to Mike Rice, chairman and CEO of BioLife, "The launch of our BloodStor product family supports our mission to become the leading provider of preservation tools for cells, tissues, and organs. Specifically, our BloodStor product offering should enable BioLife to more quickly capture a larger share of the demand for preservation media products used in the rapidly growing cord blood banking industry. We’re leveraging our Quality System and the capacity of our recently validated internal manufacturing facility to offer more standard and custom products to our strategic markets. We’ve already received orders for BloodStor 55-5 and expect to begin customer shipments by the end of September."

The company expects to achieve the ISO13485 medical device quality management systems certification by the end of 2009. As described on their website, "All BloodStor products are tested for sterility to USP 71, endotoxin to USP 85, pH, appearance, and cell-based preservation efficacy."

As further described on the company’s website, "BioLife Solutions develops, manufactures and markets patented hypothermic storage/transport and cryopreservation media products for cells, tissues, and organs. The Company’s proprietary HypoThermosol and CryoStor platform of biopreservation media products are marketed to academic research institutions, hospitals, and commercial companies involved in cell therapy, tissue engineering, cord blood banking, drug discovery, and toxicology testing. BioLife’s GMP products are serum-free and protein-free, fully defined, and pre-formulated to reduce preservation-induced, delayed-onset cell damage and death. Comprehensive small animal intravenous safety studies have been completed on HypoThermosol and CryoStor, and both products are supported by US FDA Master Files. BioLife’s enabling technology provides research and clinical organizations significantly enhanced post-preservation cell and tissue viability and function."

BioLife Solutions will be presenting and exhibiting the BloodStor 55-5 at the AABB (American Association of Blood Banks) annual meeting and TXPO (for transfusion and cell therapy professionals), to be held on October 25-27 of 2009 in New Orleans.

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.