The Glasgow-based stem cell company ReNeuron has been granted approval to begin clinical trials with its ReN001 product in the treatment of human corneal blindness. Approximately 20 patients will participate in the study, in which they will be treated with ReN001, which contains fetal stem cells harvested from aborted fetal tissue.

The trial will be conducted by Dr. Bal Dhillon and colleagues at the Princess Alexandra Eye Pavilion in Edinburgh, in collaboration with the Gartnavel General Hospital in Glasgow. According to Dr. Dhillon, “This study is the first of its kind anywhere in the world and it is exciting to be involved in such groundbreaking work. I probably see two or three new cases of corneal disease every month. On a larger scale, it’s a significant problem.”

Although preclinical animal studies were successful in testing the product, there are still a number of concerns among scientists, doctors and patients alike over the safety of fetal stem cells, not the least of which is a concern over the risk of teratoma (tumor) formation, in addition to immune rejection, biological contamination and genetic mutation, among other problems. It is precisely because of medical risks such as these that requests to begin similar human clinical trials in the U.S. were denied by the FDA.

Successful preclinical studies in animals are not always an accurate indication of a succesful therapy for humans, a prime example of which was the tragedy in the 1950s of thalidomide, the teratogenic effects of which were not evident in animal studies, although in humans approximately 10,000 children with severe malformities were born throughout the world to mothers who had taken thalidomide as an antiemetic to combat morning sickness during pregnancy. Precisely because of egregious preclinical failures such as the thalidomide disaster, from which victims suffered throughout their entire lives with extreme and untreatable deformities, the U.S. FDA remains justifiably cautious in its insistence upon proof of safety as well as efficacy before new therapies are allowed to advance to the human clinical trial stage.

Meanwhile, in the United Kingdom, ReNeuron has received permission from the U.K. Medicines and Healthcare Products Regulatory Agency to begin human testing of its proprietary fetal stem cell product, the cells of which have been expanded from the brains of aborted human fetuses and will now be injected directly into the affected areas of the brains of stroke victims, in the hopes of regenerating neural tissue. The clinical trials will consist of 12 patients divided into 4 groups of 3, who will be administered the fetal stem cells between 6 and 24 months after having suffered a stroke. The first injection will contain approximately 2 million fetal stem cells, with subsequent treatments being increased to 20 million fetal stem cells per injection. Follow-up will include monitoring for a year.

According to Dr. Keith Muir, who will lead the clinical trial, “If it works, as it has done in animal model systems, it may allow new nerve cells to grow, or regeneration of existing cells and actual recovery of function in patients who would not otherwise be able to regain function.”

The procedure remains highly controversial not only because of the scientific and medical concerns already cited above, but for ethical reasons as well. Nevertheless, from a purely scientific perspective, the U.S. FDA is not the only organization in which individuals have expressed their doubts and concerns about the safety of embryonic and fetal stem cells, since many scientists who work in private industry do not wish to waste money on the development of a therapy that might never yield a profit, and similarly many physicians do not wish to risk being sued for malpractice by treating their patients with a “therapy” that is known to cause tumors. Additionally, an increasingly savvy and informed patient base is also aware of the fact that adult stem cell therapy already exists and does not pose any of the risks that are inherent in embryonic and fetal stem cells, neither of which have even been tested yet as a clinical therapy for humans. Even if the fetal stem cells are proven to be capable of regenerating damaged neurological tissue in humans in the upcoming clinical trials, that alone is not enough to win approval as a therapy, since safety must also be proven. Neither safety nor efficacy by itself is a sufficient condition for therapeutic viability, though both together constitute a necessary condition. There is not much point, however, in pursuing a therapy in which the risks outweigh the benefits – especially when an alternative option, namely, adult stem cell therapy, already exists and is already in clinical use and has already been proven not to carry any risk of teratoma formation nor any of the other risks that are inherent in embryonic and fetal stem cells.

ReNeuron was originally spun-off from the Institute of Psychiatry at King’s College London in 1997. At the news of its approval to begin human clinical trials with fetal stem cells, ReNeuron’s stock jumped 174%, from £2.75 to £7.88, after having fallen precipitously from its 52 week high of nearly £20 per share in March of 2008.

Scientists in Brazil have used adult stem cells harvested from umbilical cord blood to treat muscular dystrophy.

Rather than referring to one disease, the term “muscular dystrophy” actually refers to a group of hereditary disorders of genetic origin and varying severity, depending upon the degree to which the dystrophin gene is defective or absent. Located at Xp21, the dystrophin gene codifies dystrophin, an essential component in the protein complex that is responsible for the membrane stability of muscle cells. A complete absence of the gene causes more severe forms of the disease such as the Duchenne form (DMD), whereas the presence of a defective gene causes milder forms of the disease such as the Becker form (BMD).

In this study, which was condcuted by Dr. Tatiana Jazedje and colleagues at the Human Genome Research Center in Sao Paulo, Brazil, the scientists took CD34+ adult stem cells derived from umbilical cord blood and established co-cultures which combined the stem cells with myoblasts from a patient who had been diagnosed with DMD. The CD34+ stem cells were already known to differentiate into muscle cells and to express dystrophin in vivo, but Dr. Jazedje and her colleagues were the first to show that this particular progenitor cell is also capable of regenerating muscle dystrophin in vitro, as the stem cells were found to have differentiated into mature myotubes after 15 days, while dystrophin-positive regions were also detected through immunofluorescence analysis.

As the authors concluded in their article, “Our findings showed that umbilical cord blood CD34+ stem cells have the potential to interact with dystrophic muscle cells restoring the dystrophin expression of DMD cells in vitro. Although utilized within the context of DMD, the results presented here may be valid to other muscle-related therapy applications.”

Stanford University scientists have announced the discovery of adult stem cells that are located in human testes and which exhibit a capacity for differentiation that appears to be similar to that of embryonic stem cells.

The discovery is the result of studies that were conducted on 19 men who were treated for infertility by Dr. Paul Turek of San Francisco. Testicular tissue samples that were obtained from the men yielded abundant quantities of stem cells which were later found to exhibit multipotency in their differentiation capability when injected into mice.

The discovery is similar to previous reports that were published in the journal Nature by a team of scientists at the University of Tubingen in Germany, who had reported similar results from stem cells isolated from the testes of mice and which were found to differentiate into a variety of mouse tissue types. This latest study, however, is among the first to be conducted in humans.

According to Dr. Renee A. Reijo-Pera, who led the team of scientists, “We have a battery of tools now and we’re moving rapidly down the long road toward their use in human medicine. I’m really amazed at the progress the science is making, and I’m certain we’ll be ready for clinical trials of some stem cell therapies within the next 5 to 10 years.”

According to Alan Trounson, president of the California Institute for Regenerative Medicine, the primary focus of which is funding for embryonic stem cell research, “This is extremely interesting and important work.”

Whether or not men will be eager to donate testicular tissue for the harvesting of stem cells, however, is yet to be seen.

Scientists in the U.K. have been forced to stop their research with human-animal hybrid experimentation because of a lack of research funds.

Less than a year after the controversial laboratory techniques were legalized in the U.K., funding agencies are now refusing to finance the research of human-animal hybrids. Although Britain has enjoyed the status of a world leader in this field, it is now feared that existing research projects may be brought to a final and permanent end within weeks.

The experimentation has proven to be highly controversial from an ethical perspective, since it fuses human cells with nonhuman mammalian eggs in a laboratory process which thereby creates a new species and a new living creature which is simultaneously both yet neither human and nonhuman. Numerous ethical debates over the procedure are still raging, and may or may not be a direct cause of the current funding drought. No specific explanation was given for the lack of funds, other than “competition” from other projects.

Two of the three license holders who are legally permitted to create hybrid embryos in the U.K. have been denied research funds, namely, Dr. Stephen Minger of King’s College London and Dr. Lyle Armstrong of the Center for Life at Newcastle University. The third license holder, Professor Justin St. John of Warwick University, is still in the process of preparing a grant proposal.

According to Dr. Minger, whose work has not yet started, even a year after his license was issued, “The problem has been a lack of funding. We haven’t been able to buy equipment, £80,000 to £90,000 worth. We put in a grant proposal last year but it wasn’t successful and we’re dead in the water. We’re discussing whether it is worth the time to re-submit our application. People reviewing grants may be looking at this from a completely different moral perspective, and how much that has influenced people’s perception about whether this should be funded, we don’t know.”

Dr. Armstrong of Newcastle University, who has created 278 hybrid embryos from human cells that were fused into cow ova, is now unable to continue working with the part-human, part-bovine embryos due to having been denied funding. According to Dr. Armstrong, “It seems a lot of effort for nothing. We are investigating other avenues to keep this work going but it is depressing that Britain seems happy to create a nice regulatory environment for this work but then not to provide money for it.”

The licenses were originally issued by the Human Fertilisation and Embryology Authority through the Human Fertilisation and Embryology Bill, which allowed for the legal creation of animal-human hybrid embryos for stem cell research and which was passed after much debate by Parliament in May of 2008 and backed by both Gordon Brown and David Cameron.

Apparently, even though the British Parliament may have finished debating this topic, it would seem as though the rest of the populace has not.

Scientists have made a discovery with adult stem cells in the fruit fly, Drosophila melanogaster, which may have important implications for humans.

In a study led by Dr. Michael Buszczak, formerly of the Department of Embryology at the Howard Hughes Medical Institute Research Laboratories in Baltimore, Maryland, and currently in the Department of Molecular Biology at the University of Texas Southwest Medical Center in Dallas, researchers have reported the identification of a protease-encoding gene in Drosophila which is commonly required in germline, epithelial and intestinal stem cells.

Known as the histone H2B ubiquitin protease “scrawny” (scny) gene, the gene encodes a ubiquitin-specific protease and is a common requirement in stem cells within diverse tissue types, since such stem cells share the common need for a chromatin configuration that promotes self-renewal. Chromatin proteins contain the genetic instructions that direct cell function, and are known to regulate multiple types of stem cells.

Among other effects, Dr. Buszczak and his colleagues observed that mutant fruit flies who lacked functional copies of the scrawny gene suffered a premature loss of stem cells in various tissue types which included their skin, intestinal and reproductive tissue.

As the authors conclude in their paper, “Our findings suggest that inhibiting H2B ubiquitylation through ‘scny’ represents a common mechanism within stem cells that is used to repress the premature expression of key differentiation genes, including Notch target genes.”

Although the scrawny gene has only been identified in fruit flies thus far, similar genes are suspected of performing similar functions in other multicellular organisms such as humans. According to Dr. Allan C. Spradling, director of the Carnegie Institution’s Department of Embryology, “Our tissues and indeed our very lives depend upon the continuous functioning of stem cells, yet we know little about the genes and molecular pathways that keep stem cells from turning into regular tissue cells – a process known as differentiation. This new understanding of the role played by scrawny may make it easier to expand stem cell populations in culture, and to direct stem cell differentiation in desired directions.”

This is not the first time that important clinical therapies for people have been developed from research conducted on the humble fruit fly. Indeed, the unpretentious Drosophila melanogaster has played a central role in the advancement of human medical science for over the past century, ever since the American geneticist and embryologist, Dr. Thomas Hunt Morgan, began studying the common fruit fly in 1906 while at Columbia University. Although a few other scientists prior to Dr. Morgan had conducted experiments with Drosophila, Dr. Morgan became the first person to demonstrate, by studying successive generations of the fruit fly, that genes are transmitted from parents to offspring via chromosomes, which constitute the molecular mechanism of heredity. Such a discovery established the foundation for the entire field of modern genetics, and Dr. Morgan was awarded the 1933 Nobel Prize in Physiology or Medicine, “for his discoveries concerning the role played by the chromosome in heredity.” Later, when Dr. Morgan relocated to the California Institute of Technology, he established the Division of Biology at Cal Tech which subsequently produced 7 Nobel Prize winners. To this day, in honor of Dr. Morgan and over half a century after his death in 1945, the Genetics Society of America still awards the annual Thomas Hunt Morgan Medal to one of its members, for outstanding contributions to the field of genetics. As a direct result of Dr. Morgan’s discoveries, Drosophila melanogaster continues to serve as a “model organism” of study for genetics and developmental biology, and as such this fruit fly has yielded a number of important discoveries that are applicable to a variety of other species, not only humans. Currently Drosophila is still being studied as a genetic model for many of the most perplexing of human diseases such as diabetes, cancer, and a number of the neurodegenerative diseases including Alzheimer’s, Huntington’s and Parkinson’s diseases, among others.

Like all other species – whether flora or fauna, vertebrate or invertebrate – fruit flies have stem cells too. Unlike many species, however, fruit flies also exhibit a number of traits that lend themselves desirably toward scientific investigation, such as a fast reproductive cycle within a short lifespan, an ease of culturability in large numbers, and a genotype in which mutations are easily inducible and easily trackable by phenotype from one generation to the next. All things considered, fruit flies make a much more compliant and cooperative laboratory specimen to study than humans.