Scientists at the University of Piitsburgh have announced today the awarding by NIH (the National Institutes of Health) of two separate grants totalling more than $5 million. One of the grants is for the study of embryonic stem cell differentiation, while the other is for investigating a new method of growing adult stem cells on lymph nodes.

Specifically, the $2.9 million, five-year "Transformative R01" grant was awarded to Dr. Eric Lagasse, professor of pathology at the University of Pittsburgh’s School of Medicine and a researcher at the McGowan Institute for Regenerative Medicine. Funding from T-R01 has been designated for the study of a novel method of "using the body’s many lymph nodes as sites for growing replacement cells for other tissues and organs, in essence using them as bioreactors to grow cells within the living body," as described in the press release.

The second grant, in the amount of $2.2 million and entitled "New Innovator", has been awarded to Dr. Ipsita Banerjee, professor of chemical and petroleum engineering and Pitt and also a researcher at McGowan. Funding from Dr. Banerjee’s "New Innovator" award has been designated to study exactly which chemical and molecular signals are involved in determining how embryonic stem cells differentiate.

As Dr. Lagasse explained, "Our regenerative medicine approach for healing damaged tissues and organs might not have moved forward without this new grant concept. This funding supports assessment and rapid translation from the bench to the bedside of nontraditional treatments."

As Dr. Banerjee added, "I want to take a completely different approach to addressing the complex process of cell development, which will potentially advance our understanding of regenerative medicine and stem cell bioengineering as a whole."

The two grants were presented as part of the 2009 NIH "Director’s High-Risk Research Awards", which are a cluster of five-year grants awarded by NIH. This year’s cluster of 115 grants constitute $348 million in total, which include 42 separate T-R01 Awards, 18 separate "Pioneer Awards", and 55 separate "New Innovator Awards" for early-stage investigators.

As described in the press release, "This marks the inaugural year for the T-R01 grants, which support innovative and high-risk projects that could profoundly impact biomedical research and medical treatment, and also is a record year for the number of New Innovator and Pioneer Awards bestowed. Fellow New Innovator and T-R01 recipients include researchers from the Cleveland Clinic, Columbia University, Duke University, Harvard University, Johns Hopkins University School of Medicine, Massachusetts General Hospital, the Massachusetts Institute of Technology, Mount Sinai School of Medicine, Stanford University, and the University of Pennsylvania."

Lava Man, the 8-year-old gelding who retired from racing last year, is now returning to racing and indefinitely postponing his retirement after showing significant improvement from autologous adult stem cell therapy.

Having dominated the California handicap division for the better part of 2 years, winning 7 Grade 1’s and earning $5.2 million in the process, Lava Man was forced into retirement last fall due to "declining form" which was caused by recurring ankle problems. Now, after having undergone several months of autologous adult stem cell therapy, the horse is showing improved physical condition, his ankle is no longer bothering him and he was able to return to the track two weeks ago for the first time in over a year.

Administered by Dr. Doug Herthel of Alamo Pintado Equine Medical Center, the monthly stem cell procedure was found to successfully regenerate cartilage in Lava Man’s ankle, thereby allowing him to begin light exercise in the spring and summer. According to the horse’s trainer, Doug O’Neill, "Training was part of the study, which we agreed to. He’s been in training for three months, and they have been raving about him." Prior to receiving the adult stem cell therapy, Lava Man was scheduled for retirement at Old Friends in Kentucky, but the retirement has now been postponed indefinitely due to the horse’s significant improvement and resumption of his racing career. Owners Steve Kenly and Jason Wood have confirmed that the horse is now noticeably ready and eager to return to racing. As Kenly stated, "He was telling us, don’t send me to Kentucky. This horse wants to train, probably more so than most horses."

Acquired by STD (Steve, Tracy and Dave Kenly) Racing Stable in August of 2004 for $50,000, Lava Man showed initial improvement with his new trainer O’Neill and went on to sweep the 2006 Grade 1 handicap races in California, which included the Santa Anita Handicap, the Hollywood Gold Cup, and the Pacific Classic at Del Mar. A 3-time winner of the Gold Cup, Lava Man last raced in July of 2008, returning to Hollywood Park in September of this year, and is now continuing to progress noticeably.

As Kenly explains, "We have his best interests in mind, and if he tells us anytime he doesn’t want to do this, that’s it," adding, "Either he competes at the highest level, or nothing."

According to O’Neill, if Lava Man is able to return to a full racing career such as that which he had previously enjoyed, then O’Neill would personally donate all of his trainer purse earnings to the racehorse retirement foundation CARMA.

The autologous adult stem cell therapy that Lava Man has been receiving would seem to indicate that the horse will not be ready for retirement for quite some time.

In a growing effort to increase public awareness of the importance of storing adult stem cells that are derived from umbilical cord blood, the Cord Blood Registry (CBR) of California has designed a web-based, online education program for the general public.

Results of recent data reflecting dismal public ignorance about stem cells were presented at an international meeting on stem cell science and policy, at which particular emphasis was given to a proprietary, web-based education system developed by the CBR which is specifically designed to help improve public awareness about adult stem cells in general, and about cord blood preservation options in particular. Although the term "stem cells" is commonly and casually thrown around by the general public on a routine basis, there are very few members of the nonscientific lay public who actually understand the scientific facts of stem cells. For example, despite continued efforts by government agencies, consumer advocacy groups and private industry to educate the public about the medical benefits of banking cord blood stem cells, 9 out of 10 expectant mothers still do not bank their child’s umbilical cord blood at all. This web-based education system marks an important step in addressing and hopefully correcting this growing problem.

In a survey of people who had completed the education program, 93% indicated that the program had improved their understanding of stem cells, while 95% indicated that they were highly satisfied with the overall program. Additionally, the CBR invited physicians, nurses and other healthcare providers to provide feedback on the program, and reviews have been submitted by nearly 7,000 individuals from these fields. According to Kelly Harkey, M.D., M.P.H., an obstetrician and gynecologist, "It’s great to finally have an up-to-date, easy-to-understand resource to direct my patients to as they are weighing their cord blood options. Because educating patients about cord blood is encouraged in my state, it’s nice that at the end of the program patients are able to confirm they’ve been educated, which ensures my practice is compliant with state legislation."

According to Heather Brown, vice president of scientific and medical affairs at the CBR, "The goal of this cord blood education program is to help physicians and other labor and delivery specialists provide expecting parents with scientifically accurate information in a compelling format, so they can make an informed choice about the options for preserving their newborn’s cord blood stem cells. This web-based system offers many advantages in that it is accessible at any time of day, it’s easily shared with spouses and other family members, and can provide documentation of the patient’s education and informed choice, especially where public policy encourages or requires education."

As early as 2005, the Institute of Medicine (IOM) had recommended that pregnant women should be educated early in their pregnancies on the value of cord blood stem cells, in order to be able to make an informed decision about cord blood banking. Thus far, however, only 17 states have passed laws that implement the IOM guidelines on cord blood education.

Adult stem cells derived from umbilical cord blood are among some of the most versatile and potent of all types of stem cells, yet they lack the inherent risks and dangers that characterize embryonic stem cells and even iPS cells. Furthermore, umbilical cord blood stem cells have already accumulated a well documented clinical history, having been used in the treatment of nearly 80 different diseases to date.

The online program is divided into categories which include descriptions of cord blood stem cells as well as the collection and storage processes, the use of cord blood in current medical treatments, recent and ongoing developments in new therapies, and storage options that are available to expectant parents. Video segments accompany the content along with personal stories from familes who describe how the banking of their own cord blood has impacted their lives.

As the world’s largest stem cell bank, the Cord Blood Registry is focused on the collection, processing and cryopreservation of adult stem cells that are collected from the umbilical cord blood of healthy, full-term newborns. CBR is accredited by the AABB (the American Association of Blood Banks) and is the family cord blood bank most recommended by obstetricians. As described in their press release, "The company has been profitable and cash flow positive from operations on a cumulative basis since 1999. CBR has processed and stored cord blood units for more than 300,000 newborns from around the world and has released more client cord blood units for specific therapeutic use than any other family cord blood bank. CBR is the leader in research and development efforts in collaboration with the world’s leading clinical researchers focused on advancing regenerative medical therapies using a child’s own cord blood stem cells. The company continues to enhance its industry-leading technical innovations for stem cell collection, processing and storage that optimize quality and cell yield."

If the public is unaware of such facts, however, then it’s a bit difficult for anyone to benefit from the availability of such services.

Hopefully, the "Online Patient Education Center for Cord Blood Banking", which may be viewed at www.cordblood.com/learn, will bring these facts to the attention of more people.

As media outlets around the world reported this latest development in stem cell technology, the opening line of a U.S. News & World Report article began by posing the following question: "If you had a brain malady that could be treated with stem cells, how would you like them delivered – by having surgeons cut open your skull to implant the cells, or by snorting them like a nasal decongestant?"

Anticipating that the latter option might be more appealing than the former, a scientist at the University of Minnesota has shown that stem cells suspended in a fluid rapidly migrate to the brain when inhaled through the nose.

Dr. William Frey, adjunct professor of pharmaceutics in the College of Pharmacy at the University of Minnesota at St. Paul, in collaboration with colleagues in Tuebingen, Germany, has developed a new stem cell "delivery method" which has applications not only for stem cells but also for other therapeutic cells and drugs that cannot easily penetrate the blood-brain barrier.

The researchers demonstrated the method in an animal model in which mice were able to sniff small droplets of fluid in which adult stem cells that had been derived from rats were suspended. Within an hour, the rat stem cells were clearly detectable within the brains of the mice. In a second experiment, rats sniffed a fluid suspension of cells from human brain tumors, which were also found to penetrate the brains of the rats within an hour.

As Dr. Frey explains, "We proved you could noninvasively deliver stem cells to the brain from the nose. We’ve shown these cells reach the brain intact."

Dr. Frey and his collaborators have filed a patent application for the invention of this "stem cell delivery technology", which works by transmitting the stem cells via the olfactory nerves of the nose and the small holes that are found in the cribriform plate, which is a thin horizontal section of the skull at the base of the brain. The olfactory bulbs that lie just above the cribriform plate are, in fact, anatomical extensions of the brain.

When researchers combined the stem cells with the enzyme hyaluronidase, which makes connective tissue more permeable, the efficiency of the migrating stem cells increased. When the enzyme was not administered, only 584 stem cells out of 300,000 reached the olfactory bulbs, whereas that number tripled when the enzyme was administered. The enzyme did not improve the ability of the stem cells to reach the cerebral cortex or other areas of the brain, however.

According to Frey, "When you cut into the brain, that leads to an inflammatory response. We’re hoping this will help. We didn’t see evidence that intranasal stem cell treatment caused inflammation. Intranasal delivery of therapeutic cells could potentially benefit the treatment of head injury, stroke, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and so on. One of the best ways to treat patients may be with their own cells. For example, the patient’s own bone marrow-derived stem cells could be delivered to produce dopamine, the missing chemical messenger in Parkinson’s disease. Therefore, we are also looking into the use of antibiotics, anti-inflammatories, and immunosuppressants that may further facilitate the safe delivery of therapeutic cells."

The next step is to test the intranasal stem cell therapy in an animal model of Parkinson’s or other types of neurological diseases, testing not only for efficacy but also for safety, especially side effects such as inflammation, infection or immune rejection.

The U.S. company Neuralstem announced today that it has won approval from the FDA to begin clinical trials for the testing of its adult stem cell therapy as a treatment for ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig’s disease.

According to Neuralstem, Phase I of the clinical trial will involve injection of its proprietary adult stem cell product directly into the grey matter of the lumbar area of the spinal cord of human patients who are suffering with varying degrees of the disease. The target enrollment is twelve patients who will be given between 5 and 10 injections of Neuralstem’s patented adult stem cell product. Data from the trial are expected in approximately 2 years.

Dr. Eva Feldman, director of the University of Michigan Health System ALS Clinic and the Program for Neurology Research and Discovery, will lead the trial. According to Dr. Feldman, "In work with animals, these spinal cord stem cells both protected at-risk motor neurons and made connections to the neurons controlling muscles. We don’t want to raise expectations unduly, but we believe these stem cells could produce similar results in patients with ALS."

It has been estimated that approximately 30,000 people suffer from ALS in the United States alone, with approximately 7,000 new cases diagnosed each year. Currently conventional medicine offers no known cure for ALS, which is a fatal disease characterized by progressive paralysis. With the advent of regenerative medicine, however, adult stem cells may prove to be the first actual therapy which not only reverses the course of the disease but which also regenerates damaged neurological tissue.

Although Neuralstem holds a number of patents for embryonic stem cell methods and processes in animal models, the company’s human stem cell product does not involve embryonic stem cells but instead is based exclusively upon adult stem cells that are derived from human adult CNS tissue.

Following today’s announcement of the FDA’s approval of the trial, Neuralstem’s stock increased 57%, or 21 cents, closing today at $2.08.

With corporate headquarters in Rockville, Maryland, Neuralstem was founded in 1996 by the current president and CEO, Richard Garr, J.D., and Merrill Solomon. As stated on their website, Neuralstem describes itself as "a biotherapeutics company utilizing its patented Human Neural Stem Cell technology", which "allows for the isolation of CNS (central nervous system) stem cells from tissue; the expansion in vitro of each cell up to a billion billion times (60 doublings), and the controlled differentiation of the cells into mature, physiologically relevant human neurons and glia."

(Please see the related news article on this website, entitled "Neuralstem Awarded Adult Stem Cell Patent", dated September 9, 2009).

Researchers at the Fourth Military Medical University in Xi’an, China, have successfully bioengineered artificial skin using adult stem cells derived from bone marrow. The new skin was tested in an animal model, where it was found to exhibit less wound contraction and better healing as well as better blood vessel development than other types of skin grafts. Applications of this new type of skin include not only therapies for wounds and burns but even organ reconstruction.

As one of the latest advances in tissue engineering, the new skin was tested in an animal model using pigs, whose skin is histologically similar to that of humans. The artificial skin was bioengineered in the laboratory with adult stem cells derived from bone marrow, and was then grafted to the animals where the dermal layer began to regenerate and the stem cells naturally differentiated into new skin tissue.

As the body’s largest organ, skin provides a number of functions which include serving as a physical barrier to disease as well as offering protection from external damage, in addition to performing certain chemical functions such as regulating body temperature. If seriously damaged from disease or burns, however, skin does not easily heal itself, and burn victims often die of secondary complications such as infection or the loss of blood plasma. Skin grafts were originally developed to address this problem, but now adult stem cells represent a significant improvement over conventional skin grafts.

In fact, the applications of this new type of skin extend far beyond dermatological uses. As Dr. Yan Jin of the Fourth Military Medical University and a coauthor of the study states, "We hope that this so-called ‘engineered structural tissue’ will someday replace plastic and metal prostheses currently used to replace damaged joints and bones by suitable materials and stem cells."