The salamander has incredible regenerative ability. In addition to ability to grow back severed limbs, salamanders have profound plasticity of neurons and can regrow severed nerve endings at a much higher efficiency than mammals. Given that we live in an age where every gene of the body is known (genomics), almost every major protein is sequenced (proteomics), and more recently the majority of small molecules have been elucidated (metabolomics), one of the major pushes in research is to use this knowledge to understand old mysteries such as the regenerative ability of salamanders.

A multi-institutional scientific team in cooperation with the University of Florida McKnight Brain Institute’s Regeneration Project received a $2.4 million National Institutes of Health Grand Opportunity grant to study regenerative process of the Mexican axolotl salamander with the aim of applying biological lessons learned to spinal cord injury.

Dr. Edward Scott principal investigator for the collaborative grant and director of the McKnight Brain Institute’s Program in Stem Cell Biology and Regenerative Medicine stated "The axolotl is the champion of vertebrate regeneration, with the ability to replace whole limbs and even parts of its central nervous system. These salamanders use many of the same body systems and genes that we do, but they have superior ability to regenerate after major injuries. We think that studying them will tell us a lot about a patient’s natural regenerative capacities after spinal cord injury and nerve cell damage."

Discoveries in other species have been a critical part of biomedical research. For example, the process of RNA interference, which won the Noble Prize in Medicine for 2006 was actually discovered as a phenomena in Petunia Flowers. The toll-like receptors, which revolutionized medical knowledge of how the immune system works were originally identified in fruit flies. The current project seeks to find molecules associated with regeneration and to attempt to replicate them first in animals and subsequently in humans.

The multidisciplinary "Regeneration Project" team is also supported by private foundations such as the Thomas H. Maren Foundation and the Jon L. and Beverly A. Thompson Research Endowment, the UF Office of the Vice President for Research, and an anonymous donor.

The use of embryonic stem cells has generally been a subject of ethical discussion and debate. On the one hand the argument is made that sacrificing a human life should never be performed to potentially save another. On the other hand some believe that the fertilized eggs from which embryonic stem cells are extracted from are not human life and therefore there should be no issue. Unfortunately, such discussions have overshadowed the public image of "stem cells", and examination of potential medical adverse effects of embryonic stem cells often is ignored in public discussions. One example of politics overshadowing medical facts may be the hastily granted FDA approval of Geron to begin human clinical trials with embryonic stem cells, an approval that was granted on the same day as President Obama’s Inauguration and then subsequently retracted.

The company Geron, located in Menlo Park and originally founded by Michael West, has been working in the area of regeneration for more than a decade. It was Geron that controls the intellectual property for the life-extending molecule telomerase, and it also was Geron that funded the studies which resulted in creation of human embryonic stem cells. One product that Geron chose to develop is human embryonic stem cells that are differentiated into nervous system cells, for use in treatment of patients with spinal cord injury. While it is common knowledge to scientists but not to the public that embryonic stem cells cause cancer, Geron through treating the cells with various chemicals, believes it has generated a cellular product that does not pose the risk of cancer.

After numerous animal experimentations, including small and large animals, Geron was granted FDA approval for a Phase I clinical trial in 10 patients that had spinal cord injury within 7-10 days. This approval was linked to political motives by some. According to Robert N. Klein, the chairman of California’s $3 billion stem cell research program, "I think this approval is directly tied to the change in administration," said He said he thought the Bush administration had pressured the F.D.A. to delay the trial.

The approval was withdrawn in August, 2009 before any patients were treated. The trial was placed on what is called "clinical hold", meaning that patients cannot be treated until more data is submitted. This was because some animals in the studies were seen to develop abnormal cysts.
In the press release today, Geron stated that subsequent to their recent discussions with the FDA, they believe they will have sufficient new animal data to allow for continuation of the trial sometime in thei third quarter of 2010.

RNL Biostar Inc., a subsidiary of the Seoul-based company RNL Bio Inc., has been based in Rockville, Maryland since 2006. Now, in addition to its facility at the Technology Development Center, it plans to add a new facility in Germantown, worth $6 million, to which the company also plans to add 50 newly hired employees over the next 3 to 5 years. The new positions will include manufacturing technicians and lab personnel in addition to administrative personnel. According to Donna Lee, director of business development at RNL, "There will be pretty big growth spurts because of the amount of work we have."

The new RNL facility will be converted from an already existing structure, which currently occupies nearly 10,000 square feet and comprises a combination of labs and office suites. RNL Biostar projects that its facilities will occupy 20,000 square feet by 2014.

Currently RNL is in Phase II clinical trials for the testing of its proprietary adult stem cell products for the treatment of osteoarthritis and Buerger’s Disease, which is an inflammatory and blood clotting condition. Additionally, the company has received FDA authorization to commence clinical trials with its adult stem cell product in the treatment of spinal cord injury, which are scheduled to start at the end of the year.

RNL’s proprietary products are formulated from adult stem cells that are harvested from adipose (fat) tissue. According to Ms. Lee, "In Maryland, the fat samples come to our lab here first. People send in their fat and we extract stem cells out of the fat and ship them in nitrogen tanks to Korea, where cells are cultured and multiply. We have helped a lot of people with rheumatoid arthritis with a one-time IV injection. It’s really amazing to watch."

However, the U.S. citizens who donated their own adipose-derived adult stem cells must travel to China or Japan for the injections, since such treatments are not allowed in the U.S., due to a severely antiquated FDA.

RNL has also developed a stem-cell-based hand cream.

In the latest chapter of the ongoing saga over the first clinical trial ever to be conducted with human embryonic stem cells (hESCs), a new delay has presented itself.

Specifically, representatives of the Geron Corporation have announced today that U.S. federal regulators have placed a halt on the clinical trial that Geron was scheduled to conduct, before even one patient could be enrolled in the study.

Although a number of people among the non-scientific communities have expressed surprise over what they consider to be an unexpected announcement, there are many among the scientific community who find such a delay to be completely unsurprising and even predictable.

Frought with doubts and problems from the very start, the clinical trial was intended to use hESCs in the treatment of spinal cord injury. Because it would have been the first such study ever to be conducted with hESCs, the proposed clinical trial has repeatedly been the subject of widespread speculation and controversy. Now, this new ruling by the FDA, which brings all the momentum of the entire project to a grinding halt, has merely incited a new round of speculation and controversy.

The U.S. federal regulators decided to impose a halt on the clinical trial as a direct result of new data that Geron disclosed to the FDA, regarding dose escalation in preclinical animal studies. In January of this year, the FDA lifted an additional halt that it had previously imposed on Geron in May of 2008. This time, the new halt is based on safety concerns triggered by the new higher-dose data.

According to Joseph Pantginis, an analyst with the Merriman Curhan Ford Group in New York, "They are at the forefront, which a lot of times is a bit of a curse. They have to hit all the hurdles and be the first one to learn about how these cells behave."

In an official statement issued by representatives of Geron, the company "will work closely with the FDA to facilitate their review of the new data and to release the clinical hold."

Anna Krassowska, a spokesperson for Geron, stated to the press that the company had no further comment.

The news release posted on Geron’s website was brief, at only two paragraphs in length, not counting the customary "forward-looking statements" and "safe harbor" disclaimers. As stated on the comapny’s website, "GRNOPC1, a cell therapy for neurologically complete, subacute spinal cord injury, has been placed on clinical hold by the FDA pending the agency’s review of new nonclinical animal study data submitted by the company. A clinical hold is an order that the FDA issues to a sponsor to delay a proposed trial or to suspend an ongoing trial. … No patients have yet been treated in this study."

As the New York Times article concludes, "While thousands of patients around the world have been treated with adult stem cells and have shown mixed results, no humans have been given cells derived from embryos in an approved trial."

Indeed, it would seem as though, once again, embryonic stem cells remain confined to the experimental, laboratory stage, unable to progress to clinical trials. Meanwhile, by comparison, numerous types of adult stem cells have already advanced to Phase III clinical trials and beyond, and in fact have already been in use as viable therapies in clinics around the world for years.

Dr. Feng Lin, director of research at Bio-Matrix Scientific Group and its subsidiary Entest Biomedical, believes that traumatic brain injury (TBI) could possibly be cured with autologous adult stem cells derived from adipose (fat) tissue.

According to Dr. Lin, "Currently there is no effective therapeutic approach to reverse the initial brain damage caused by trauma. Brain cells or neurons have limited ability for self-repair and spontaneous axonal regeneration. Extensive studies have been focusing on novel therapeutic strategies for traumatic brain injury. In my opinion, adipose-derived stem cells could possess the capacity for self-renewal and differentiation into diverse cell types such as neural cells. We could be looking at an exciting and potential cure for traumatic brain injury patients."

Both Bio-Matrix and Entest Biomedical are currently studying the ability of adipose-derived stem cells (ASCs) to regenerate damaged neurological tissue and to repair the inflammation and brain ischemia that result from TBI. Together, Bio-Matrix and Entest have recently submitted a research proposal to the U.S. Army Medical Research and Material Command (USAMRMC) for funding to investigate an ASC therapy for TBI, which is a common problem among U.S. soldiers returning from Afghanistan and Iraq, where roadside explosives are a frequent cause of TBI. According to reports from the Walter Reed Army Medical Center in Washington, D.C., sustained TBI is found in nearly a third of all returning soldiers who have combat injuries.

According to David Koos, chairman and CEO of Bio-matrix, "The objective of our proposal is to develop an effective ASC-based (adipose-derived stem cell) therapy for TBI. Specifically, we will substantially study the therapeutic effect of ASCs on TBI-associated brain ischemia and inflammation via intravenous administration or by intro-cerebral transplantation. It is plausible that our proposed study will pave the way for an ASC-based therapy for TBI, which hopefully will be much more feasible and safer than other stem cell-based approaches."

Headquartered in San Diego, Bio-Matrix Scientific Group is involved in the design and development of the next generation of medical devices and instrumentation including non-invasive bio-systems monitoring devices, adult stem cell cryogenics and instruments for tissue management. A wholly owned subsidiary of Bio-Matrix Scientific Group, Entest BioMedical is involved in the development of testing procedures for diabetes, and in the development of stem cell applications to diabetes and other diseases.

Every 15 seconds, throughout the world, someone suffers a brain injury. For people who suffer permanent brain injury, the average cost of lifetime care and rehabilitation is in the millions of dollars per person. According to one of the leading researchers in the field, Dr. Tracy McIntosh of the University of Pennsylvania School of Medicine, "Sadly, it is an epidemic that most people do not realize exists, and to date, there is no clinical treatment that can effectively treat the damage." Another leading researcher in TBI, Dr. Ronald Hayes, director of the University of Florida Brain Institute, concurs by stating, "Currently no effective treatment exists."

TBI affects more people than stroke or Alzheimer’s disease combined. It is the leading cause of death in Americans under the age of 45, and it is also the leading cause of long-term neurological disability in children and young adults. According to the website of the National Institute of Neurological Disorders and Stroke (NINDS), a division of the National Institutes of Health (NIH), "Traumatic brain injury is a major public health problem, especially among male adolescents and young adults ages 15 to 24, and among elderly people of both sexes 75 years and older. Children aged 5 and younger are also at high risk for TBI." The Brain Injury Association of America defines TBI as follows: "A traumatic brain injury is defined as a blow or jolt to the head or a penetrating head injury that disrupts the function of the brain. Not all blows or jolts to the head result in a TBI. The severity of such an injury may range from ‘mild’, i.e., a brief change in mental status or consciousness, to ‘severe’, i.e., an extended period of unconsciousness or amnesia after the injury. A TBI can result in short or long-term problems with independent function."

Also known as "acquired brain injury", or simply "head injury", TBI is a type of "neurotrauma" that has been estimated to occur in approximately 1.5 million people per year in the United States alone. Of those, approximately 1.1 million cases per year are considered mild and are treatable in hospital emergency rooms, while approximately 235,000 cases per year are considered moderate and result in extended hospitalization, and approximately 50,000 cases per year are fatal. These figures are believed to be conservative estimates, as the actual number of people who sustain TBIs but who do not seek medical treatment is unknown. According to the U.S. Centers for Disease Control and Prevention (CDC), there are currently more than 5.3 million Americans who are living with some form of long-term or lifelong injuries that were incurred from TBI.

Reliable global statistics for TBI do not exist, although the World Health Organization has issued the following statement on the subject: "Neurotrauma is a critical public health problem that deserves the attention of the world’s health community. Estimates of brain and spinal cord injury occurrence indicate that these injuries cause enormous losses to individuals, families, and communities. They result in a large number of deaths and impairments leading to permanent disabilities. Research has also shown that traumatic brain injury usually requires long-term care and therefore incurs economic costs to health systems. For this reason, many countries need to develop surveillance systems and conduct epidemiologic studies to measure the impact of neurotrauma among their people to guide the development of more effective preventive methods. A number of methods have already proven effective, such as the use of motorcycle helmets, head supports in vehicles or on sports equipment." Among members of the military who have been deployed to war zones, and also among reporters who are assigned to cover such wars, blasts are the leading cause of TBIs. For military medical personnel who may be involved in the triage, treatment, and transport of such combat-related injuries, a publication entitled "Guidelines for the Field Management of Combat-Related Head Trauma" is available from the Brain Trauma Foundation, at www.braintrauma.org. The guidelines were compiled by a group of civilian and military experts from the fields of neurosurgery, trauma and EMS who were assembled by the Brain Trauma Foundation for the specific purpose of formulating such guidelines that would address the particular nature of war-related head injuries. The publication was funded by the Defense and Veterans Brain Injury Center in collaboration with the Henry M. Jackson Foundation for the Advancement of Military Medicine. Among the civilian population of the U.S., approximately half of all TBIs are caused by motor vehicle traffic accidents, and approximately half of all TBIs involve the use of alcohol. Outside of war zones, therefore, TBIs are among the most preventable of injuries. Between the ages of 15 and 24, males are nearly twice as likely as are females to sustain a TBI. For people aged 75 and older, most TBIs are the result of falls. Approximately 20% of all TBIs are due to violence, and approximately 3% are the result of sports injuries. Over 90% of TBIs that are caused by the use of firearms result in death, whereas approximately 11% of TBIs that are caused by falls result in death. As of 1995, combined direct medical expenses and indirect costs such as lost productivity from work due to TBI was estimated at $56.3 billion in the United States.

Adult stem cell therapy offers the first type of treatment for TBI which can actually heal the injuries by regenerating damaged neurological tissue.

(Please see the related section on this website, entitled, "Traumatic Brain Injury", located under "Research").

In response to President Obama’s March 9th Executive Order, the U.S. National Institutes of Health (NIH) have issued the first draft of a set of guidelines suggesting how federal funds should, and should not, be used for human embryonic stem cell research. The scientific, medical and religious communities have eagerly awaited the release of these guidelines, which have been highly anticipated, and debated, by all.

Specifically, the guidelines state that federal funds may now be used for research conducted on any human embryo that is “stored” at an IVF clinic and which is considered to be “spare”, “left-over”, or “orphaned”, after having been originally created at an IVF (in vitro fertilization) clinic for reproductive purposes. In other words, researchers may now apply for NIH grants to pay for such research – NIH grants being one of the primary, though certainly not the only, source of biomedical research funding throughout the United States. Nevertheless, contrary to public misconception, the NIH guidelines still prohibit the use of federal funds for research conducted on human embryonic stem cells derived from human embryos that were created by other means and for other objectives, such as, for example, somatic cell nuclear transfer, parthenogenesis, therapeutic cloning, and in vitro fertilization specifically designated for research or experimental, not reproductive, purposes.

It has been estimated that approximately 500,000 human embryos are currently frozen in a state of perpetual “limbo” in freezers at IVF clinics throughout the U.S., and many people, including the legal parents of these frozen “orphaned” embryos, are wondering what should be done about the situation. If any of the embryos were to be implanted into the uterus of an adult human female, many of the embryos would develop into a normal fetus and would ultimately be born as a human child, although some percentage of the embryos would either fail to implant properly or would fail to develop normally and would therefore not result in a healthy birth. When a woman solicits the services of an IVF clinic, usually for reasons pertaining to infertility, in order to be implanted with an embryo that was created through in vitro fertilization, it is standard procedure for the doctors of the IVF clinics to create multiple embryos with the IVF technique, precisely because of the fact that not every embryo will successfully implant and develop into a normal, healthy birth. The consequence of this routine, unquestioned practice is the creation of an unseen population of approximately half a million human embryos that nobody wants and which are destined either to be frozen indefinitely, discarded as biological trash, or now, as a result of the new NIH guidelines, deliberately destroyed in the process of embryonic stem cell research. The ethical can of worms that has been unleashed merely by the fact that these “orphan”, frozen human embryos exist, is beyond the scope of this news article to address, and possibly even beyond the scope of NIH to address. However, certainly one of the topics which NIH has yet to define precisely are the legal terms and conditions of the consent forms that parents of these frozen embryos must sign before their embryonic offspring can be officially designated for laboratory research and destruction.

Regardless of the specific legalities, embryonic stem cell scientists will now be allowed to receive federal funding (i.e., from NIH) for research which they may now perform on any of these “orphan” human embryos that are available from IVF clinics, all of which were originally created for reproductive purposes in the hopes of creating a human child, but which are “no longer needed for that purpose,” according to NIH acting director Dr. Raynard Kington. Although there are approximatley half a million orphaned human embryos frozen in IVF clinics across the U.S., it has been estimated that only approximately 700 new stem cell lines from those embryos would now be available for human embryonic stem cell research. Certainly 700 represents a significant increase from the number of human embryonic stem cell lines that were initially available in 2001 for federally funded research under the Bush administration, which originally had been estimated in the 60s but later proved to be numbered in the 20s. It is a common misperception, however, that President Obama has made broad, sweeping changes that will suddenly allow for any type of human embryonic stem cell research, as this is not the case, or at least not yet. The creation of human embryos specifically for research, not reproductive, purposes, is precisely what embryonic stem cell scientists covet the most, yet the federal funding of this type of research still remains illegal under the Obama administration, at least so far. Many proponents of adult stem cell research fear, however, that even this policy may, in time, change.

The new NIH guidelines allow for federal funding to be used for the very thing that is banned by the Dickey-Wicker Amendment, namely, research in which the health or life of a human embryo is threatened or destroyed. Although many people expect the Dickey-Wicker Amendment to be formally overturned at some time during the Obama administration, these NIH guidelines represent a concrete and immediate step in that direction. If Congress does, in fact, rescind the Dickey-Wicker Amendment, then the legalization of therapeutic cloning and other scientifically dangerous as well as ethically controversial procedures are seen as the logical next step. According to bioethicist Wesley Smith, “The political campaign has begun to destroy the Dickey Amendment. Should that happen, it would be legal for the Feds to fund human cloning, the making of embryos for research, and just about anything ‘the scientists’ wanted to do in this regard. Once that happens, the NIH would likely revise these guidelines to permit funding for those activities… Expect the struggle over Dickey to erupt within the next few years during the annual budgetary process. And if a bill passes sans the Amendment, there is no question in my mind that Obama would sign it.”

President Obama’s March 9th Executive Order directed NIH to submit guidelines addressing both the scientific and the ethical concerns of human embryonic stem cell research, within 120 days of that Executive Order, and NIH has issued this eagerly-awaited first draft in slightly over a month. According to NIH acting director Dr. Kington, “We considered the range of ethical issues and we believe this policy will allow the substantial research that is ethically responsible and scientifically worthy. We believe this is our best judgment now about a reasonable policy at this time.”

Apparently, a number of people disagree with Dr. Kington, such as, for example, Tony Perkins, president of the Family Research Council, who states, “The NIH draft guidelines demanded by the President will do nothing to advance stem cell research that is showing near-term benefit for suffering patients. Instead of funding more embryo destructive research, the government should fund research using adult stem cells that are on the cutting edge of treating patients for diabetes, spinal cord injury, heart disease and various cancers. Unfortunately, this draft guidance only diverts limited federal resources to unethical stem cell research that has not successfully treated a single person for any disease.”

Although embryonic stem cell proponents like to think that Obama’s policy on expanding embryonic stem cell research is a sign of “progress”, already Obama’s embryonic stem cell policy would appear to be outdated. It was nearly two years ago, on September 21st of 2007, that Dr. James Thomson was quoted in the Boston Globe as stating, “The world has changed. Over time, these [iPS] cells will be used in more and more labs. And human embryo stem cell research will be abandoned by more and more labs.” Dr. Thomson, of course, was the first person ever to isolate an embryonic stem cell in the laboratory, first in 1995 from a nonhuman primate and then in 1998 from a human. The entire field of embryonic stem cell research exists, therefore, purely as a result of Dr. Thomson’s achievements, and his name is revered in stem cell laboratories throughout the world. If anyone would understand the future direction of embryonic stem cell research, it would be Dr. Thomson. By sharp contrast to embryonic stem cells, the recently developed iPS (induced pluripotent stem) cells hold much greater research and clinical potential than do embryonic stem cells. Furthermore, since iPS cells can be created without involving an embryo at all, let alone destroying an embryo, iPS cells do not involve any of the ethical dilemmas that are inextricably entangled in embryonic stem cell research. Additionally, Dr. Ian Wilmut, who created the world’s first cloned mammal, Dolly the sheep, was quoted in Time magazine in December of 2007 as stating, “Changing cells from a patient directly into stem cells has got so much more potential”, once again referring to the advantages of iPS cells when compared to embryonic stem cells. Along those same lines, Dr. Shinya Yamanaka, who first developed iPS cells, was quoted in the December 11th, 2007 issue of the New York Times as stating, “We can’t keep destroying embryos for our research. There must be another way.” Apparently, neither President Obama nor the distinguished scientists at NIH have sought the advice of any of the world’s foremost leading authorities on embryonic stem cell research, cloning, nor iPS cells.

As stated on the website of the NIH, “The purpose of these draft Guidelines is to implement Executive Order 13505 on March 9, 2009, as it pertains to extramural NIH-funded research, to establish policy and procedures under which NIH will fund research in this area, and to help ensure that NIH-funded research in this area is ethically responsible, scientifically worthy, and conducted in accordance with applicable law. Internal NIH procedures, consistent with Executive Order 13505 and these Guidelines, will govern the conduct of intramural NIH research involving human stem cells.” This first set of guidelines by NIH is only a draft, which will be published next week in the Federal Register where public comments from the general population will be accepted for the next 30 days. As also stated on the NIH website, “The National Institutes of Health (NIH) is requesting public comment on draft guidelines entitled ‘National Institutes of Health Guidelines for Human Stem Cell Research’ (Guidelines).” Apparently, members of NIH believe that it is possible for scientific and bioethical matters to be decided democratically, by majority opinion. Based upon the input of these public opinions, NIH is then expected to issue a final set of guidelines by early July.

(Please see the related news articles on this website, entitled, “Former Director of NIH Explains Why Embryonic Stem Cells are Obsolete”, dated March 4, 2009; “Obama Decrees Changes in Embryonic Stem Cell Research, Though Not What One Might Expect”, dated March 9, 2009; “Obama Rescinds Bush-Era Executive Order Pushing for More Ethical Stem Cell Research”, dated March 10, 2009; “Obama Signs Law Restricting Federal Funding of Embryonic Stem Cell Research”, dated March 11, 2009; “A High-Profile Proponent of Embryonic Stem Cell Research Sharply Criticizes Obama’s Policy”, dated March 13, 2009; and “Members of The President’s Council on Bioethics Object to Obama’s Stem Cell Policy”, dated March 26, 2009).