Underreported Obstacles to and Issues with Potential HESC Therapies

I promised a post on Human Embryonic Stem Cell Research. These are some under-reported problems I made note of two years ago, after I attended an NIH training course. Updates are included where relavent.

• Unless scientists find economically feasible ways to regulate the process by which HESC’s differentiate into specific cell types and unless contaminants can be reliably eradicated, the development of therapies is questionable. Yi E. Sun, a neural stem cell researcher at UCLA [at the time of the 2005 NIH course], called the technique for deriving pure oligodendrocytes (a type of neural stem cell) developed by Reeve-Irvine Research Center scientist Hans Kierstead “a little bit magicish.” Both instructors and students at the NIH course expressed awe that Keirstead could spend $20,000 a month keeping his cell lines healthy.
• Stem cell transplants produce an immune response that can either cause the stem cell graft to attack the recipient —thus requiring the patient to submit to a life-long regimen of potent anti-rejection drugs; or, the patient’s immune system can destroy the stem cell graft. Immune response is a primary factor behind the push toward therapeutic cloning (Somatic Cell Nuclear Transfer–SCNT). Theoretically, stem cells derived from a donor egg and a patient’s somatic (e.g. skin) cell would carry the nuclear genome of the patient and therefore do not cause an immune response.
• However, recruiting enough egg donors is both unrealistic and exploitive. The discredited Korean scientists extracted 242 eggs from 16 women to create one stem cell line. Keirstead said that SCNT is unlikely to lead to therapies because each clone would be a unique biologic requiring FDA approval. [He now is touting SCNT and is moving in this direction himself at UC Irvine.] However, the possibility of problems like disease transfer from donor eggs hasn’t been resolved according to Doug Wallace, director of molecular and mitochondrial medicines and genetics at UC Irvine. This is because there are two genomes in the human body—nuclear and mitochondrial, and the mitochondrial genome is inherited from the mother, i.e. the egg donor. (Prostate cancer is primarily a mitochondrial disease.) The good news about SCNT according to course director Phil Schwartz, is that it proves that reprogramming of adult stem cells is possible. [The better news is that papers have since been published proving adult stem cells can be reprogrammed, thus elimnating the need for HESC therapies altogether.]
• Melissa Carpenter, a former director of stem cell biology and scientific director of regenerative medicine at the HESC giant Geron Corporation, observed aneuploidy—a gain and/or loss of chromosomes that while sometimes harmless can also be carcinogenic—in cell lines that had been in culture for “a couple years.” Carpenter said she was not at liberty to discuss “differences” that exist in Geron Corporation’s lines because Geron doesn’t want those differences published. Geron funded the initial derivation of HESCs at the University of Wisconsin and [at the time of my interview with him] funded Keirstead’s research at $500,000 per year. The company holds at least two patents (5,843,780 and 6,200,806) with UW’s stem cell research institute (WiCell).
• The WiCell procedure manual reported recovery of HESC colonies after thawing frozen cryovials at .1-1 percent. Thus improved cryopreservation techniques would be necessary before Keirstead’s vision of frozen vials of HESCs available for implantation in emergency rooms across the country is viable.
• According to patent attorney Cathryn Campbell, not only is the technique for deriving stem cells patented by WiCell, but the HESCs themselves are patented. WiCell appears to be utilizing a technique by which patent holders file successive patents so that none ever fully runs out. U.S. researchers who develop HESC therapies are currently subject to WiCell’s patents, even, theoretically, if they develop their own lines. This means that therapies aren’t likely to reach patients until multimillion dollar patent challenges make their way through the courts. [The patent board is currently reviewing this issue.]
• Andrew Pollack, a business writer for the New York Times who primarily reports on the biotech industry expressed skepticism that the biotech sector will propel the field forward. He said the industry was skittish about the profitability of cell therapy, noting that BayBio, the San Francisco Bay area biotech consortium, didn’t endorse Proposition 71 until days before it appeared on the November 2004 ballot. [Proposition 71 also reportedly includes a little known provision providing substantial kickbacks to phramaceutical companies for any therapies that are developed. Perhaps this is why the biotechs finally signed off on the measure.]
• In 2004, Emily Niemitz and Andrew Feinberg of Johns Hopkins School of Medicine reported a link between assisted reproductive technologies and heritable malformations. They also noted a two-fold increase in major birth defects. The duo concluded, “In this era of heightened involvement of institutional review boards in even minimally invasive research, it is surprising that there is a lack of such surveillance in developing methods for creating and culturing human embryos intended for birth.” No one yet knows if these mutations would be significant for potential Hesc transplant recipients, but it’s long past time for regulation in the human embryo industry.

http://christineascheller.wordpress.com/2007/06/26/ethics-interrupted