Refinements in Stem Cell Transplants Continue
May 27, 2011 - A ground-breaking new study has used stem cells derived from skin to restore vision in experimental animals – and a young Canadian scientist has played a critical role. The study, at Harvard’s prestigious Schepens Eye Research Institute, used “induced pluripotent stem cells” (ipSCs)” created by reprogramming skin cells. When the cells were transplanted into the eyes of mice with a retinal degenerative disease, they repaired large areas of the damaged retinas. Some of the transplanted cells became part of the recipient retina, which became responsive to light as a result. With further refinement, similar transplants might eventually be used to restore sight to people with retinitis pigmentosa, age-related macular degeneration, or other retinal degenerative diseases.
"We are very excited about these results," says Dr. Budd A. Tucker, first author on the study, which was published in the journal PLoS ONE. "While other researchers have been successful in converting skin cells into induced pluripotent stem cells (ipSCs) and subsequently into retinal neurons, we believe that this is the first time that this degree of retinal reconstruction and restoration of visual function has been detected." Dr. Tucker obtained his PhD at Newfoundland’s Memorial University in 2006 and was completing his scientific training at Harvard with the support of a FFB post-doctoral fellowship when he worked on this study.
Japanese scientists first showed that stem cells could be generated from skin cells in 2006. Dr. Tucker and his mentor, Dr. Michael Young, used the Japanese techniques to generate ipSCs and then applied additional chemical coaxing to create retinal precursor cells. Even after this treatment, about 30% of the cells remained as undifferentiated stem cells, but the scientists developed additional techniques to remove the undifferentiated cells so that they would not grow into tumours. Drs. Young and Tucker then transplanted the purified precursor cells into the eyes of blind mice. They observed that within four to six weeks the transplanted cells took up residence in the photoreceptor layer of the eye, becoming part of the degenerated retina and restore it into healthy-looking retinal tissue. The team used non-invasive functional testing (electroretinogram, ERG) to demonstrate that the new photoreceptor cells could send signals to other neurons, which then generated electrical responses when exposed to light.
The techniques used by these scientists, to select appropriate cells for transplantation, are an important advance. IpSCs cells are desirable for transplanting. Because they are not scarce and ethically controversial embryonic cells, the source cells can be cheaply and easily collected from the patient or a donor. Many challenges remain, however. For one, although the mice in this study remained tumour-free after 98% of the undifferentiated cells had been removed, the risk of tumours due to the remaining undifferentiated cells would be unacceptable in human therapy. Second, to use the patient’s own cells as source for ipSCs (and thus reduce the risk of immune rejection), an additional step will have to be introduced to repair any mutations in the patient’s mutant genes with healthy ones. Third, the transplants were successful in only 6 of the 10 mice that received transplants; in the other four, the transplanted cells were found to have died after transplantation, for reasons that are not yet known.
Although further investigations are clearly needed before this approach can be used therapeutically in humans, this study is one of several recent works that suggest a growing potential for ipSCs transplants. Another recent study has demonstrated that gene mutations in ipSCs cells can be genetically corrected before transplantation, opening the possibility that a person’s own cells could be the source of sight-restoring replacements – even if they have a genetic condition such as retinitis pigmentosa.
This research is another indication of the rapidly accelerating pace of scientific discovery, which seems likely to produce practical therapies to combat blindness in the not too distant future. Your support of the Foundation Fighting Blindness makes such advances possible.
To learn more about stem cell research, please review our stem cell research factsheet.