The California-based conglomerate Healthcare of Today has announced its acquisition of the Houston-based biotech company Regenetech for $100 million. Among Regenetech’s several hundred patents and patent applications throughout the world are 13 patents licensed from NASA for the expansion of adult stem cells in the type of microgravity environment that exists throughout interstellar space.

According to the CEO of Healthcare of Today, Henry Jan, “Regenetech’s work is astounding. We are thrilled to bring a leader in adult stem cell technology into the family of Healthcare of Today companies. Our mission has always been to provide the highest levels of healthcare to our clients, and a company whose passion is to do this through biotechnology is a natural fit for us.”

Founded in May of 2008 and headquartered in Burbank, California, Healthcare of Today is a holding company, the primary focus of which is the acquisition and development of diverse types of corporations within the healthcare industry. The Regenetech acquisition is merely the latest in a series of acquisitions made by Healthcare of Today, which in recent weeks has also made other corporate purchases of similar size and significance. Through its various subsidiaries, Healthcare of Today owns a number of pharmaceutical, insurance, assisted living, senior communities, nurse staffing, real estate brokerage and biotechnology businesses.

Regenetech, which boasts at least one NASA astronaut among the members of its scientific advisory board, is a leader in the R&D of adult stem cells. In September of 2008, Regenetech entered into a technology and patent licensing agreement with Biogenea-Cellgenea of Greece for the development of adult stem cell therapies in the treatment of cardiovascular, hematological and neurological diseases including Parkinson’s disease, Alzheimer’s disease and spinal cord injuries.

According to their website, Regenetech “develops and offers intellectual property licenses in the area of adult stem cell expansion and therapeutic applications of adult stem cells. Regenetech uses a technology discovered by NASA in space experiments for growing three-dimensional (3D) stem cells in a weightless environment. Regenetech’s research results indicate that adult stem cells can be harvested from a filtered extraction of the patient’s own blood and grown to larger, therapeutic quantities eliminating the most critical problem in conventional adult stem cell therapies: availability of adult stem cells rapidly, safely, and at reasonable cost. This minimally invasive procedure reintroduces the patient’s own stem cells to provide red and white blood cells, platelets, and connective tissues. Regenetech has the exclusive rights to thirteen patents originally issued to NASA. The company has added to the original technology licensed from NASA through its own technology creation program and has to date filed applications for over 200 patents of its own with additional patent applications targeted.”

It has long been well known that ordinary cells throughout the body are easily damaged by radiation, while cancer cells are not. For this reason, cancer patients who undergo radiation therapy often suffer from the destruction of their healthy tissue, whether or not the radiation is also successful in destroying the cancer cells. Radiation is not always successful in destroying cancer cells, however, and the reasons behind this fact have remained elusive, until now.

In collaboration with the City of Hope National Medical Center, researchers at the Stanford University School of Medicine have found a possible solution to this problem. Studying breast epithelial stem cells from humans and mice, the scientists discovered a “protective pathway” that shields normal stem cells from DNA damage. Unfortunately, this molecular defense mechanism is also a characteristic of some types of cancer stem cells; fortunately, however, when this pathway is blocked, the cells become more susceptible to radiation.

The protective pathway consists of the increased expression of proteins that bind and deactivate the various types of reactive oxygen species (ROS) which damage DNA. The scientists found that normal stem cells, such as stem cells of blood and breast epithelial origin, have lower levels of ROS than do regular cells which are not stem cells. Similarly, cancer stem cells also have lower levels of ROS since the cancer stem cells produce a higher level of the antioxidant proteins than do non-stem-cell cells. The antioxidant proteins in turn intercept and deactivate the ROS before cellular damage has been incurred. In non-stem-cell cells, this protective mechanism poses a distinct advantage, while in cancer stem cells it is a distinct disadvantage. Cancer stem cells with low ROS levels were found to be twice as likely to survive a course of ionizing radiation than were other tumorous cells that had higher levels of ROS.

The discovery of the protective protein expression now offers a new approach to cancer treatment: the scientists found that blocking the generation and activation of the protective proteins makes the cancer stem cells more susceptible to radiation, especially when glutathione is blocked, as this is one of the strongest of all antioxidants. Of course, it is important to block the protective protein expression only in the cancer stem cells, and not also in the normal, noncancerous and non-stem-cell cells.

According to Dr. Michael Clark, associate director of the Stanford Institute for Stem Cell and Regenerative Medicine and the original discoverer of the first cancer stem cell in a solid tumor, “The resistance observed in the breast cancer stem cells seems to be a similar if not identical mechanism to that used by normal stem cells. Although your body would normally eliminate cells with chromosomal damage, it also needs to spare those cells responsible for regenerating and maintaining the surrounding tissue – the stem cells. It’s protective. Basically, we need to figure out a way to inactivate that protective mechanism in cancer cells while sparing normal cells.”

As Dr. Robert Cho adds, “Our ultimate goal is to come up with a therapy that knocks out the cancer stem cells. If you irradiate a tumor and kill a lot of it but leave the cancer stem cells behind, the tumor has the ability to grow back,” which in fact is exactly what often happens, thereby leading to relapses in patients months or even years after a seemingly successful treatment. Although the debate over the exact origin of cancer stem cells has not yet been put to rest, there is no debate over the fact that cancer stem cells, even in very small quantities, can reconstitute an entire tumor cell population, and the natural resistance of these cells to conventional medical therapies such as radiation has continued to pose a major dilemma to oncologists and their patients. Now, there may be at least a partial solution.

According to radiation oncologist and post-doctoral fellow Maximilian Diehn, M.D., Ph.D., “Since cancer stem cells appear to be responsible for driving and maintaining tumor growth in many tumors, it is critical to understand the mechanisms by which these cells resist commonly used therapies such as chemotherapy and radiotherapy. Ultimately, we hope to improve patient outcomes by developing therapeutic approaches that directly target cancer stem cells or that overcome their resistance mechanisms.”

Scientists at the University of California at San Diego have discovered how to combine nanotubes with adult stem cells to accelerate bone growth.

In what represents yet another novel convergence of previously disparate fields, namely, medicine and the strictly inorganic field of materials science, bioengineers have taken mesenchymal stem cells that were derived from bone marrow and grown them on the tops of very thin titanium oxide nanotubes. Such a procedure, the scientists discovered, allows for greater control over the differentiation of the stem cells. More specifically, it is by varying the dimensions of the nanotubes that selective differentiation of the stem cells can be induced, such as, for example, into osteoblasts for the repair of injured bone. Simply stated, the larger the diameter of the nanotube, the larger the resulting elongation of the surface of the stem cells when compared to those stem cells that are grown on narrower nanotubes.

According to Dr. Sungho Jin, a coauthor of the paper, “If you break your knee or leg from skiing, for example, an orthopedic surgeon will implant a titanium rod and you will be on crutches for about three months. But what we anticipate through our research is that if the surgeon uses titanium oxide nanotubes with stem cells, the bone healing could be accelerated and a patient may be able to walk in one month instead of being on crutches for 3 months. Our in-vitro and in-vivo data indicate that such advantages can occur by using the titanium oxide nanotube-treated implants, which can reduce the loosening of bones, one of the major orthopedic problems that necessitate re-surgery operations for hip and other implants for patients. Such a major re-surgery, especially for older people, is a health risk and significant inconvenience and is also undesirable from the cost point of view.”

Dr. Seunghan Oh, another author of the article, adds, “What we have accomplished here is a way to introduce desirable guided differentiation using only nanostructures instead of resorting to chemicals.”

As Dr. Jin further explains, “The use of nano-topography to induce preferred differentiation was reported in recent years by other groups, but such studies were done mostly on polymer surfaces, which are not desirable orthopedic implant materials.” According to Dr. Shu Chien, director of the new Institute of Engineering in Medicine at UC San Diego, “Our research in this area has pointed to a novel way by which we can modulate the stem cell differentiation, which is very important in regenerative medicine. This will lead to a truly interdisciplinary approach between engineering and medicine to getting novel treatments to the clinic to benefit the patients.”

Indeed, the field of regenerative medicine is becoming increasingly interdisciplinary, as the mere name of the newly established Institute of Engineering in Medicine suggests. The previous, erroneous paradigm in which distinct and separate scientific and medical fields are somehow expected to evolve independently of each other is demonstrably false, today more than ever before. Increasingly so, it is the cross-pollenation of ideas between disciplines which is driving the advancement of science and technology, and which is an especially vital and essential ingredient in the development of successful stem cell therapies.

Citing weakness in the bond market as a result of the recent global financial crisis, the governing board of the California Institute for Regenerative Medicine has announced that it will halt the scheduled funding of stem cell scientists at six Bay Area research laboratories. Of the $58 million in stem cell funding which has been halted, approximately $17 million was earmarked for university programs throughout California which were intended for the training of laboratory technicians, and without which many laboratories will be understaffed.

Voted into law in 2004 with the passing of Proposition 71, the California Institute for Regenerative Medicine is the agency that was specifically created for the purpose of funding stem cell research, with a high priority on embryonic stem cells, in the state of California through sources unrelated to federal tax dollars. Such an initiative was therefore perfectly legal as it did not constitute a violation of the restrictions imposed by President Bush on the use of federal tax dollars for embryonic stem cell research. However, the California Institute for Regenerative Medicine was financially structured such that its mere existence is heavily dependent upon the bond market, which has suffered seriously in recent months. Although its board members have determined that the Institute still has enough money to fulfill its grant obligations through September of 2009, the decision was nevertheless made to delay the actual distribution of funds until March, in order to assess the full extent of losses incurred to and by the bond market.

According to the original plan, the total “fiscal impact” of Proposition 71 was structured at approximately $6 billion, half of which was designated as principal and the other half of which was expected to be generated from the interest on general obligation bonds, a type of municipal bond, that would be issued to finance the funding that is to be awarded by the Institute. Although a certain percentage of the money is allocated to cover administrative expenses, the bulk of the $6 billion would then be distributed in the form of grant money at an annual average of $200 million over 30 years. Due to the current global economic crisis, however, which is the worst since the Great Depression of the 1930s, investments in a number of sectors, including the bond market, have unexpectedly evaporated in recent months.

Known as Proposition 71 and voted into California state law in 2004, the $3 billion stem cell initiative which created the California Institute for Regenerative Medicine is now being reexamined.

After encountering setbacks from a variety of sources which have included legal, economic and scientific challenges, a number of scientists are taking a second look at the embryonic stem cell initiative which was supposed to have accomplished so much but which instead has accomplished so little. As the result of a growing lack of investor confidence in embryonic stem cells, not only as a consequence of the ongoing ethical debate that surrounds embryos but also due to caution regarding the inherent medical risks that are unique to embryonic stem cells, only a small handful of companies in California are actually experimenting with embryonic stem cells. Despite predictions that Proposition 71 would create a job boom in the stem cell field which in turn would stimulate greater economic prosperity throughout the state, as well as medical cures for disease and injury, in fact the exact opposite has proven to be true, and currently the California Institute for Regenerative Medicine has even put a freeze on the distribution of its scheduled funding. Additionally, the promise of a clinical therapy ever actually being developed from embryonic stem cells seems to be an unrealistic dream that is retreating further and further away with each passing day.

According to Alan Trounson, president of the California Institute for Regenerative Medicine, “I would have expected there to be more interest.”

In 2004, proponents of Proposition 71 predicted that the new law would generate more than 2,000 jobs per year during the first 5 years, but in fact there is no demand for such jobs due to a scarcity of companies that are willing to work with embryonic stem cells. Although Geron of Menlo Park has been predominantly in the news lately, with their FDA approval for the first clinical trial ever to be conducted with human embryonic stem cells, in actuality Geron is not as large an organization as people might think, with only 140 employees according to its latest annual report. Furthermore, Geron invested more than $150 million over 13 years in preliminary research in order to win FDA approval just to begin clinical trials with embryonic stem cells, and many more years of expensive clinical trials will be required before the FDA can even consider approving the marketing of an actual therapy. Since most of Geron’s preclinical research was conducted prior to Proposition 71 and therefore prior to the creation of the California Institute for Regenerative Medicine, most of Geron’s funding came from alternate sources that were unrelated to the Institute. Even if Geron is successful in bringing a new stem cell product to market, years from now, companies such as Geron and Advanced Cell Technology hold the patents for their proprietary technology, which is a disincentive to other biotech entrepreneurs who would be at a competitive disadvantage if they were to try to enter the field. In fact, most of the $635 million distributed thus far by the California Institute for Regenerative Medicine has been awarded to university laboratories or to other nonprofit organizations for basic research on embryonic stem cells, and not to biotech companies, which have received less than $6 million from the Institute. There have also been lawsuits challenging the constitutionality of the Institute, which resulted in a further restriction on the distribution of grant money until the Supreme Court dismissed the lawsuits in May of 2007. Additionally, there remain a number of safety concerns about embryonic stem cells, especially in regard to teratomas, which are a specific type of tumor that embryonic stem cells must, by definition, form, and such concerns have cast serious doubt on the safety and efficacy of embryonic stem cells as a clinical therapy. For those few businesses which are willing to delve into embryonic stem cell research, they have found even fewer investors who are actually willing to back them, due to the unknown timeline at which a profit might ever be attainable.

According to Robert Lanza, chief scientific officer of the Los Angeles-based stem cell company Advanced Cell Technology, “Raising money has been almost impossible.” In 2006, Advanced Cell Technology relocated its headquarters from Worcester, Massachusetts to Los Angeles in order to take advantage of the state funding for embryonic stem cell research that was enacted into state law with the passing of Proposition 71. Since then, Advanced Cell Technology had been working toward the development of an embryonic stem cell therapy for diseases of the eye, but was forced to halt its research when the company encountered financial problems and adequate funding was not forthcoming.

Meanwhile, in sharp contrast to embryonic stem cells, adult stem cells are already being used as real therapies in real clinics around the world, treating real human patients with real diseases and injuries – while also paying a hefty dividend to investors. Consequently, an increasing number of scientists, investors and patients alike are turning their attention to adult stem cell therapies, since embryonic stem cells have yet to prove any therapeutic viability. Even if restrictions on federal funds are lifted by the new administration, the ethical controversies and the medical dangers, especially that of tumor formation, which are inherently problematic in embryonic stem cells, are enough to dissuade many biotech entrepreneurs from having anything to do with embryonic stem cells.

Ethics and politics aside, embryonic stem cell research is a lengthy and risky process, which thus far has been frought with dangers, scientifically as well as financially.