Can transplanted stem cells restore function and increase survival?
October 22, 2002
Investigator: Ole Isacson, MD, Harvard Medical School/McLean & Massachusetts General Hospital, Boston
Project: Implantation of HB9 GFP genetically engineered mouse embryonic stem (ES) cells to restore function in a rat model of ALS
Dr. Ole Isacson, Director of the Neuroregeneration Laboratories and Morris K. Udall Parkinson's Disease Research Center of Excellence at the McLean Hospital, will apply his expertise in transplant studies in Parkinson's disease to investigate whether stem cell transplants into a rat model of ALS will restore function and increase survival. Genetically modified embryonic stem cells (HB9 GFP ES cells) will be provided by Dr. Tom Jessell. (This work has recently been published in the journal Cell.) Research in Dr. Tom Jessell's laboratory has demonstrated that these mouse embryonic stem cells can be differentiated into motor neurons (the population of nerve cells that die in ALS) and when introduced into the spinal cord of embryonic chicks, motor axons form contacts with skeletal muscle. Introducing green fluorescent protein, GFP, enables the investigator to trace which cells have been transplanted and where the processes from these cells are going.
Transplantation studies into the rat spinal cord will be undertaken in collaboration with Dr. Martin Marsala at The University of California, San Diego. The embryonic stem cells will be transplanted into the spinal cord at different time points and the function and survival of the rats monitored. Detailed analysis of whether the cells have integrated and made contacts with host tissue will be performed. Experiments will be done to determine specific conditions that would allow for optimal integration of new neurons into the tissue.
It is currently unknown whether transplanted motor neurons will indeed successfully integrate in sufficient number in adult tissue to restore function. The promising studies in Dr. Tom Jessell's laboratory were done in embryonic tissue, which has greater potential for regeneration. Although highly enriched for stem cells that will differentiate into motor neurons, other cell types are also present in this mouse embryonic stem cell line, and these transplanted cells may provide growth factors important for maintaining the survival of the remaining motor neurons in the ALS rat model.
These studies complement ongoing efforts funded by The ALS Association and build on an already outstanding team of researchers at Wisconsin University. Su-Chun Zhang, MD, PhD, presented his promising results at a recent Cure ALS Advisory Committee meeting in New York. His continued efforts will optimize conditions for the differentiation of human embryonic stem cells in sufficient quantities for transplantation, as well as identify the molecular cues required to generate motor neurons. Clive Svendsen, PhD, in his study addresses whether fetal cells modified to produce trophic factors (required for cell survival) and transplanted into a rat model of ALS will restore function and increase the lifespan of the rat. These efforts, along with the continued collaboration between the different groups and the individual investigators, will address the many remaining challenges to moving the stem cell field forward with a goal to develop this as a potential therapy for ALS.
