Stem cell therapies for spinal cord injury

Abstract

Stem cell therapy is a potential treatment for spinal cord injury (SCI), and a variety of different stem cell types have been evaluated in animal models and humans with SCI. No consensus exists regarding the type of stem cell, if any, that will prove to be effective therapeutically. Most data suggest that no single therapy will be sufficient to overcome all the biological complications caused by SCI. Rationales for therapeutic use of stem cells for SCI include replacement of damaged neurons and glial cells, secretion of trophic factors, regulation of gliosis and scar formation, prevention of cyst formation, and enhancement of axon elongation. Most therapeutic approaches that use stem cells involve implantation of these cells into the spinal cord. The attendant risks of stem cell therapy for SCI--including tumor formation, or abnormal circuit formation leading to dysfunction--must be weighed against the potential benefits of this approach. This Review will examine the biological effects of SCI, the opportunities for stem cell treatment, and the types of stem cells that might be used therapeutically. The limited information available on the possible benefits of stem cell therapy to humans will also be discussed.

Figure 1

Rationales for stem cell transplantation in spinal cord injury repair. a,b | Stem cells can be directed to differentiate into specific lineages to replace lost or damaged cells (cell replacement). The cells can be directed to differentiate into oligodendrocytes, which can remyelinate spared axons (panel a), or into neurons to replenish the existing damaged neurons (panel b). c,d | Stem cells can be engineered to produce trophic factors that can promote survival and prevent death of damaged cells (trophic support). These trophic factors can be directed towards local cells in the area surrounding the spinal cord lesion (panel c) or directed to provide trophic support (green arrows) to neurons with axons that project down the spinal cord (panel d), such as neurons in the red nucleus in the midbrain, the axons of which project down the spinal cord as the rubrospinal tract. e,f | Stem cells can facilitate axon outgrowth. The cells can be transplanted directly into and adjacent to the lesion, which promotes axon growth and extension past the lesion (panel e). Stem cell transplants can also be designed to diminish and/or inhibit the scar tissue in the lesion, thereby reducing its inhibitory effects and promoting axon outgrowth (panel f).