Michael J Fox Changes Tune on Embryonic Stem Cells

Actor Michael J. Fox, whose acting career has included such greats as the “Back to the Future.” series, and the television series “Spin City,” and others has been diagnosed with early onset Parkinson’s disease (PD). He has also been a stalwart proponent of embryonic stem cell research. Apparently, he believes that embryonic stem cell research will provide a potential treatment for his PD and many other PD patients as well. The Michael J Fox Foundation has been a supporter of PD research, which includes embryonic stem cell research into PD treatments.

Michael J. Fox was the subject of some controversy a few years ago when he appeared in some political ads for Missouri 2006, Michael J. Fox endorsed Claire McCaskill, Democratic candidate for the senate from the state of Missouri, who is also an ardent supporter of embryonic stem cell research. In those ads, Fox told viewers in the ad that Ms. McCaskill supported stem cell research that could provide a cure for his Parkinson’s disease. There were also accusations that Fox had gone off his PD-controlling medications during the period of time the ad was shot in order to increase his symptoms and elicit sympathy. The radio talk show host Rush Limbaugh suggested that Fox could have been acting, but many people emailed Limbaugh saying that Fox typically went off his medication before testifying before Congress.

Nevertheless, Fox no longer believes that embryonic stem cell research is the sina qua non of PD treatment. In an article at the New Scientist web site, Fox stated that the problems with stem cell-based treatments made him less sanguine about the possibilities of a stem cell-based treatment for PD.  This does NOT mean that Fox is no longer a supporter of embryonic stem cell research.  It simply means that one of the most vociferous advocates of embryonic stem cell research is unwilling to place all his hope in it as a viable cure for PD.  This is truly a remarkable development.

PD has been experimentally treated with cells from aborted fetuses.  These experiments are nothing short of gruesome, and they did not provide any evidence of lasting viable cures.  Furthermore, when the brains of individuals who had received the transplants were examine postmortem, the implanted cells showed the same pathologies as the surrounding tissue.  Therefore the implants were a rousing flop.  Some successes have been seen with transplantation of animal tissue, but these experiments were few and far between, and have risks of infecting patients with animal viruses.

With respect to stem cell treatments or PD, a highly-publicized Nature paper implanted dopamine-making neurons that were made from embryonic stem cells into the brains of PD mice.  While many of the symptoms improved, the implanted cells generated lots of tumors (see Roy N et al., Functional engraftment of human ES cell–derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes, Nature Medicine 12, 1259-68; November
2006).  Wesley J Smith has noted that Fox called these tumors “tissue residue.”  This is either ignorance or dishonesty.  100% of the rats in these experiments that received that implants developed tumors.  This is not tissue residue, they are tumors.

On the other hand, adult and umbilical cord stem cells have shown some remarkable successes, as have experiments with specific proteins called “neurotrophic factors,” which stimulate endogenous brain cells wot divide and make new connections with other cells.  For example, PD rats that were treated with umbilical cord stem cells showed significant recovery in motion and behavior (Weiss ML, et al., Stem Cells 24, 781-792, March 2006).  Additionally, researchers from Kyoto University treated PD mice by transplanting nerve cells developed from their own bone marrow stromal cells (Mari Dezawa et al., Journal of Clinical Investigation 113:1701-1710, 2004).

When it comes to neurotrophic factors,  University of Kentucky scientists treated ten Parkinson’s patients with a protein called glial cell line derived neurotrophic factor to stimulate the patients’ own brain stem cells and showed significant improvement in symptoms (Slevin JT, et al., Journal of Neurosurgery 102, 216-222, February 2005).  Also British researchers injected a protein known as a “neurotrophic factor” into the brains of 5 Parkinson’s patients and found that it stimulated the patients’ own adult neural stem cells. This treatment provided an average 61% improvement in motor function (Gill SS et al., Nature Medicine 9, 589-595; May 2003).  Later autopsies of these treated patients demonstrated that the neurotrophic factors stimulated sprouting of new neurons in the brain (Love S. et al., Nature Medicine 11, 703-704, July 2005).

Likewise, all present clinical trials for PD are all adult stem cell- or induced pluripotent stem cell-based.

Another treatment for PD that is not stem cell-based is Deep Brain Stimulation (DBS).  DBS uses a surgically implanted medical device called a brain pacemaker that sends electrical impulses to specific parts of the brain.  DBS in select brain regions has provided remarkable therapeutic benefits for otherwise treatment-resistant movement disorders like PD (see Kringelbach ML, et al., Nature Reviews Neuroscience. 2007;8:623–35).

Therefore Fox was certainly right to change his perspective on embryonic stem cells. If only he would see that destroying the youngest and most vulnerable members of humanity is too high a price to pay for the cures of others.  There are better and more humane and ethically-sound ways to treat PD, and those ways are being pursued.

Regenerated Hair from Adult Stem Cells

Japanese researchers led by Takashi Tsuji from the Research Institute for Science and Technology at Tokyo University of Science have made bioengineered hair follicle germ cells from adult epithelial stem cells and dermal papillae cells. These hair follicle germ cells form functional hair follicles and grow hair. This is a proof-of-concept experiment for bioengineered organ replacement that may then proceed to human clinical trials.

These bioengineered follicle germs were made with epithelial and mesenchymal stem cells from skin found on the backs of mouse embryos (stage E18 for those who are interested). Once these cells were dissociated, they were combined with stem cells from adult hair follicles (the bulge region).

In a previous paper, Tsuji’s lab showed that a bioengineered hair follicle germ that was reconstituted from embryonic follicle germ-derived epithelial and mesenchymal cells could generate a bioengineered hair follicle and shaft if they used their new technique (Nakao, K. et al. The development of a bioengineered organ germ method. Nat. Methods 4, 227–230 (2007)). However, the Nature Methods paper did not transplant these bioengineered hair follicles into the skin of laboratory mice to determine if they could produce fully functional hair regeneration that includes hair shaft elongation, hair cycles, connections with surrounding tissues, and the regeneration of stem cells and their niches.

In this recent publication, Tsuji’s co-workers in his lab rigorously established that these bioengineered hair follicles could do everything a naturally produced hair follicle could do. In order to direct the growth of the hair toward the surface of the skin, Tsuji and others used a tiny plastic container with a fine nylon thread in the middle to direct the growth of the hair shaft. Previous experience had shown that implanting the bioengineered hair follicles into the skin caused them to form “epithelial cysts,” or fluid-filled vesicles that did not form hairs. The reason for this abnormal behavior is that the implanted follicles are connected with the surface of the skin, and therefore, lack polarity. The small, plastic containers provides a surface upon which the cells can grow toward the skin surface, and the nylon thread directs the extension of the hair shaft toward the skin surface.

These hair follicles expressed all the right genes and also cycled the way normal hair follicles cycle (growth of the hair, cessation of growth, dumping the hair shaft, and then regrowth of the hair shaft). This study definitely demonstrates the ability of adult tissue-derived follicular stem cells to serve as bioengineered organ replacements therapies.