Summary: Researchers at the San Raffaele Hospital (Milan, Italy) published landmark results of studies in which they successfully injected adult mouse neural stem cells to promote tissue repair and clinical recovery in mice with MS-like disease:
These exciting results, if confirmed, represent an early but significant step forward in efforts to find a way to repair nerve tissue damage that may be relevant in people with MS;
These results must be viewed with caution, given the differences between mice and humans, and the problem of identifying donor cells that would not be rejected by recipients’ immune systems;
Further studies are necessary to confirm these results, and to address the issues involved in translating such experiments into studies in humans with multiple sclerosis.
Details: Researchers report that immature nerve cells (adult mouse neural stem cells, or neurospheres) injected into the blood or brain cavities of mice with MS-like disease can move throughout the brain and spinal cord to sites of tissue damage, promote repair of nerve-insulating myelin, decrease damage to nerve fibers, and reverse clinical disease. Stefano Pluchino, MD, and colleagues (San Raffaele Hospital, Milan, Italy) report their pathbreaking findings in the April 17 issue of Nature (2003;422:688-694). If confirmed, this success in lab animals represents a significant step forward in the effort to find a way to repair nerve tissue damage in people with MS.
Background: In recent years, scientists have been exploring ways to repair the damage of brain and spinal cord tissues during the course of the immune attack in MS. Evidence suggests that the body does successfully repair some myelin damaged in MS, but not enough to keep up with its loss. Research has shown that adult brains contain stem cells – also known as precursors or progenitors – that might serve as replacement cells. It has been hoped that, given the right signals, these may be stimulated to grow into viable new tissue.
Studies involving transplantation of immature myelin-making cells (oligodendrocyte precursors) have been successful in rodent models, triggering recovery of function and restoring nerve conduction. However, such repair has only been successful in isolated areas of the brain, whereas MS and MS-like diseases in animal models involve lesions scattered throughout the brain and spinal cord. Finding a way to introduce potential replacement cells that can migrate throughout the central nervous system and home in on damaged areas has presented a significant hurdle in this field.
Dr. Pluchino’s team and others have been investigating transplantation of neural stem cells, which have the potential to develop into various types of brain cells – including nerve cells and myelin-making cells – and which appear capable of expanding their numbers extensively, and moving to distant sites of injury within the brain.
The Study & Results: Dr. Pluchino and colleagues took adult neural stem cells from mouse brains and grew them in the lab, and then injected them into the blood or ventricles (hollow spaces within the brain) of mice with EAE, a chronic, MS-like disease. They “tagged” the donor cells so that they were able to trace their location in the host animal’s tissues. Thirty days later, many cells – transplanted by either method – had migrated to multiple areas of tissue damage, had matured into myelin-forming cells, and deposited myelin around nerve fibers. Significant recovery of nerve function, clinical recovery from symptoms, and decreases in myelin damage and nerve fiber loss were observed in mice receiving transplants, compared to control animals that did not receive the transplants. Clinical recovery occurred faster in mice receiving the transplants via the blood versus those receiving transplants via the ventricles.
Conclusions: Neural stem cells transplanted into mice with an MS-like disease were able to migrate to multiple areas of myelin and nerve fiber damage in mice with an MS-like disease, repair this damage, and restore clinical function. Clinical recovery occurred faster when cells were injected into the bloodstream, suggesting that less invasive methods of tissue repair may be possible.
These exciting results, if confirmed by other scientists, represent an early but significant step forward in the effort to find a way to repair nerve tissue damage that may be relevant in people with MS. However, these results must be viewed with caution, given the differences between mice and humans, and the significant problem of identifying donor cells that would not be rejected by the host’s immune system. Further studies are necessary to confirm these results, and to address the issues involved in translating such experiments into studies in humans with multiple sclerosis.Submitted 8/27/2003 8:18:18 PM