Feb 13, 2013
A team co-funded by the National MS Society transplanted stem cells derived from human skin into the brains of mice with a disorder that prevents them from growing new myelin, the insulating material that surrounds nerve fibers and which is damaged in MS. They found that the transplanted cells developed into myelin-making cells that formed new myelin quickly and efficiently. Su Wang, PhD, Steven A. Goldman, MD, PhD (University of Rochester Medical Center, Rochester, NY) and colleagues report their findings in Cell Stem Cell (2013;12:252). These early findings highlight a novel strategy that seems to reduce some of the risks of cell replacement strategies, but further research is necessary to establish the potential safety and effectiveness of this approach before it can be attempted in people with MS.
Background: Myelin, the substance that surrounds and supports nerve fibers, is destroyed in the brain and spinal cord during the course of multiple sclerosis. In addition, the cells that manufacture, maintain and can repair myelin, called oligodendrocytes, are also damaged and destroyed. Young oligodendrocytes known as progenitors or precursors (OPCs) can naturally develop through a series of steps into oligodendrocytes, to repair damaged myelin, but they fail to keep pace with the damage in MS. One of several possibilities being explored for repairing myelin damage is to transplant cells that could supplement these OPCs. Researchers are searching for cell types that could be transplanted safely (without immune rejection or tumor generation), could serve as an abundant source of OPCs, and could migrate to areas needing repair.
Over many years, the team led by Dr. Goldman has been exploring cell transplantation as an approach to restoring myelin in mice. The National MS Society has been supporting this work with the help of donors including the Alan Buegeleisen Fund, the Barancik Foundation, and the Society’s South Central Region. Dr. Goldman was also a member of two teams that were part of the Promise: 2010 Nervous System Protection and Repair Initiative. His previous efforts led to successful recovery of myelin function in mice. This new study explores the use of adult skin cells as a source of cells for transplantation.
The Study: The team used stem cells derived from human skin, and in the laboratory, developed a strategy for coaxing these cells to become OPCs. The strategy proved to generate sufficient numbers of OPCs for transplant. The researchers transplanted the OPCs into the brains of mice with a genetic disorder that prevents new myelin from forming. The cells traveled quickly and efficiently throughout the brain to produce myelin, and increased the likelihood of survival of the mice compared with untreated controls. No mice developed tumors during the term of the study, a potential side effect of stem cell treatments.
Comment: These studies present a novel strategy for replacing cells that fail to repair myelin. Further research is needed to confirm these findings and to explore their potential safety and benefits for repairing myelin damaged during the course of MS. An attractive aspect of this strategy is that cells for transplantation could potentially be developed from a patient’s own skin, reducing the risk of rejection by the body’s immune system, although not eliminating it completely.
Dr. Goldman is currently supported by the National MS Society for further work in this area. In addition, the Rochester team, along with the State University of New York Upstate Medical University in Syracuse and the School of Medicine and Biomedical Sciences at the University at Buffalo, recently leveraged $12.1 million in funding from New York State Stem Cell Science for clinical trials of stem cell strategies. The first study is beginning in 2015 using another type of stem cell. According to a press release from the University of Rochester, Dr. Goldman anticipates that a trial of skin-derived cells will eventually be funded via this mechanism. Read more here.