In the politicized debate about stem cell research, each side has been known to accuse the other of blindness to the ethical implications of using or not using the technology, respectively.
Following a 1995 horse-riding accident that left him paralyzed from the neck down, actor Christopher Reeve, who passed away Sunday, became a strong proponent of the ethical value of stem cell research. In an April 2000 testimony before the U.S. Senate, Reeve asked, "Is it more ethical for a woman to donate unused embryos that will never become human beings or to let them be tossed away as so much garbage when they could help save thousands of lives?"
Massachusetts biotechnology company Advanced Cell Technology also is not shy about trying to sway stem cell opponents - the company's website includes a "Take Action" page that encourages visitors to write to politicians in favor of stem cell research. Now, together with scientists from Wake Forest University and the University of Chicago, the company has published research demonstrating the generation of cells from embryonic stem cells that might have promise for treating biological blindness.
The retinal pigment epithelium is a layer of cells that have a variety of functions. Degeneration of the retinal pigment epithelium leads to degeneration of the macula (the central part of the retina, which includes most photoreceptors) and ultimately to blindness.
In their paper, which appears in the Fall 2004 issue of Cloning and Stem Cells and is titled "Derivation and Comparative Assessment of Retinal Pigment Epithelium from Human Embryonic Stem Cells Using Transcriptomics," the authors described culturing human embryonic stem cells and harvesting retinal pigment epithelium cells from the cultures. The cells showed both molecular and functional characteristics of retinal pigment epithelial cells. When the authors compared gene-expression profiles of the embryonic cell-derived cells to fetal retinal pigment epithelium cells, those profiles also were similar.
Going forward, the authors hope to test the embryonic cell-derived retinal pigment epithelium in animal models for ability to correct vision deficits.
Embryonic cells also have been used to cure congenital heart defects in a mouse model, as described in the Oct. 8, 2004, issue of Science by scientists at Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, both in New York City. The researchers reported that injection of wild-type stem cells into embryos rescued Id knockouts, which usually are lethal (the embryos die during development due to their severe heart defects). In further experiments, they showed that the rescue was due to both differentiation of stem cells into heart cells and the secretion of growth factors by the stem cells.
Remarkably, when the researchers injected those stem cells into mothers bearing mutant embryos before conception, such heart defects also were partially, though not fully, reversed. While the embryos did not die during gestation, mouse pups lived for only two days - not exactly a ripe old age, even for a mouse. Nevertheless, the research showed that, in principle, the factors secreted by embryonic stem cells can cross the placenta to exert beneficial effects from a distance.
While embryonic stem cells are clearly the most flexible stem cell type, research into stem cells derived from adult sources also is ongoing. And in a strange bit of recycling, the remnants of liposuction, which leaves plastic surgeons with well more than a ton of tissue to dispose of annually, could get a partial second lease on life. At least its stem cells could. In 2001, researchers at the University of California at Los Angeles (where there are booming markets, one assumes, for both plastic surgery and recycling) and the University of Pittsburgh first reported that fat tissue contains stem cells, which they managed to isolate and prod into differentiating into various cell types.
Last week, researchers working on such adipose-derived stem cells met in Pittsburgh at the International Fat Applied Technology Society Annual Meeting, "Targeting Fat For Therapy: New Opportunities for Translational Research and Clinical Treatment."
Adipose-derived stem cells have the capacity to turn into bone, muscle, cartilage and neural tissue, as well as more fat. "Fat is a very abundant tissue in the human body. It's very easy to remove small quantities or even large quantities of fat without major risk, and the cells that are stem cells are found in high concentrations within the fat tissue," Peter Rubin, assistant professor of plastic and reconstructive surgery at the University of Pittsburgh School of Medicine, said in a press briefing that detailed consensus statements from the conference on a number of issues relating to fat stem cells.
Fat stem cells are thought to be best suited to autologous use, at least in the near future. Keith March, professor of medicine at Indiana University School of Medicine, reported from the breakout group on clinical trials that "this field of using adipose stem cells is now poised scientifically to enter in clinical trials." Based on risk-benefit analysis, available animal data, as well as human data on affected pathways in the diseases, March named bone defect repair, peripheral vascular disease and cardiac vascular disease as the top applications.
There also was a report on the first clinical application of fat stem cells, to treat rectovaginal fistulas in patients with Crohn's disease. "When a fistula appears in patients with Crohn's disease, the clinical features are terrible," said Damian Garcia-Olmo, professor at the Universidad Aut noma de Madrid in Spain. That's hardly an overstatement, given that fecal incontinence through the vagina is just one of those clinical features. Moreover, Garcia-Olmo added, because of compromised tissue in Crohn's disease, "in these cases, there is normally not a good response to the classical medical treatment" of surgical closure.
The researchers decided to use fat rather than bone marrow stem cells because harvesting bone marrow stem cells is much more complex. Eight fistulas in four patients were treated with autologous fat-derived stem cells and then observed for at least eight weeks; closure lasting for the duration of the observation was seen in six of those fistulas. Garcia-Olmo stressed that the patients, would "never [be] cured, because of the recurrence of Crohn's disease. But we are banking the cells, and perhaps the next vaginal fistula or rectal fistula can be closed without an operation."