by John C. Martin
Article Date: 07-29-05

A new, international study suggests that stem cells, the primitive cells that give rise to cells found in the brain, could be the key to treating multiple sclerosis.1 In the study using a group of mice, researchers at the San Raffaele Hospital in Milan, Italy found that immature nerve cells known as neural stem cells injected into the animals' bloodstreams resulted in suppression of immune attacks that is believed to lie at the heart of multiple sclerosis.

Stem Cells: Myelin Protectors
The unexpected findings, if confirmed in future research, suggest that these stem cells may not only serve as replacement cells for tissue repair, but may also protect the brain from inflammation. "In central nervous system inflammation, neural multipotent precursor [stem] cells are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions," wrote Stefan Pluchino, MD, and his colleagues in the Neuroimmunology Unit at San Raffaele Hospital in Milan, Italy.

Stem cells are designed to differentiate into a wide variety of cell types in the body. They can also divide indefinitely to replenish other cells. When stem cells divide, they can remain a stem cell or evolve into another type of cell with a specialized function, such as a muscle cell.2

A New Focus
In recent years, medical experts have been experimenting with ways to repair the damage in the central nervous system that results after MS strikes. While some studies have suggested that the body successfully repairs some of the damage,3 it isn't enough. However, experts have found that the adult brain contains stem cells that might serve as replacements for the damaged tissue. Thus, at the center of the latest research have been efforts to either induce stem cells to repair damaged myelin (a fatty substance surrounding nerve cells in the brain that is a key target of the attacking immune system in people with MS) or other cells, or a possible stem cell transplant.4

While stem cell transplantation has been successful in other animal studies,5 scientists have found that repair of damaged tissue has only occurred in isolated areas of the brain, whereas MS involves lesions scattered throughout the brain and spinal cord. Thus, finding a way to introduce potential replacement cells that can migrate throughout the central nervous system and home in on damaged areas has been a significant challenge in recent years.

Relapse Reductions Noted
Most recently, Pluchino and his team have been investigating the transplantation of neural stem cells, which then differentiate into various other cells, then migrating to distant sites of injury in the central nervous system.6 In their latest research, they were attempting to define how the stem cells migrated into the brain and sites of injury.

In their study, the investigators injected neural stem cells taken from the brains of adult mice into the blood of mice with a disease similar to relapsing-remitting MS. Some mice were injected at the onset of disease and others were injected at the first sign of a flare-up.

The mice that were injected at disease onset started to recover in between 30 and 60 days, and experienced a significant reduction in the number of relapses compared to untreated mice. Mice injected at the first relapse recovered later, but showed a threefold reduction in the number of relapses between 60 and 90 days compared with mice that weren't treated.

The team also found that that a protein on the surfaces of the stem cells allows them to cross from the blood into the brain, and facilitated their movement in the brain. A wide range of immune proteins were also found on the surfaces of these stem cells that serve as "docking sites" to receive signals from immune cells involved in the attacks in the central nervous system.

A portion of the transplanted cells remain in an immature state, as well, collecting around blood vessels where immune cells enter the brain during MS. These stem cells showed signs that they were able to turn off activated immune cells and reduce inflammation, protecting brain tissues from immune-mediated damage.

"These results indicate that undifferentiated adult neural precursor cells have relevant therapeutic potential in chronic inflammatory central nervous system disorders because they display immune-like functions that promote long-lasting neuroprotection," Pluchino and his team wrote.

The findings, while optimistic, should be confirmed in larger studies, they pointed out.

1. Pluchino S, Zanotti L, Rossi B et al. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature 2005 Jul 14;436(7048):266-71.
2. National Institutes of Health. Stem Cell Basics. Available at: http://stemcells.nih.gov/info/basics/. Accessed July 25, 2005.
3. Nait-Oumesmar B, Lachapelle F, Decker L, Baron-Van Evercooren A. Do central nervous sytem axons remyelinate? Pathol Biol (Paris) 2000 Feb;48(1):70-9.
4. Jefferson S, Jacques T, Kerinan BW, Scott-Drew S, Milner R, ffrench-Constant C. Inhibition of oligodendrocyte precursor motility by oligodendrocyte processes: implications for transplantation-based approaches to multiple sclerosis. Mult Scler 1997 Apr;3(2):162-7.
5. Oka S, Honmou O, Akiyama Y et al. Autologous transplantation of expanded neural precursor cells into the demyelinated monkey spinal cord. Brain Res 2004 Dec 24;1030(1):94-102.
6. Pluchino S, Quattrini A, Brambilla E et al. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 2003 Apr 17;422(6933):688-94.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.

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