Abstract

Injury to the CNS has a devastating effect on the patients, leaving the body with serious loss of motor and sensory functions. Transplantation of stem cells provides a successful experimental therapeutic strategy to treat these CNS disorders. Clonal stem cells are reliably reproducible cells with constant features. Their possible mechanism of action is based upon a) their neuroprotective effect, b) their capacity to promote regeneration of injured axons by down-regulating the development of the non-permissive glial environment and c) to a lesser extent replacement of lost glial cells and neurons. Indeed, grafting a well characterised clonal stem cell line (NE-GFP-4C, ATCC No. CRL -2926) into the injured spinal cord results in functional and morphological improvement. Our data suggest that undifferentiated clonal stem cells secrete a variety of cytokines and some of the neurotrophic factors for a limited period of time after transplantation into the injured cord. On the other hand, some cells of graft origin appear to have been integrated into the injured cord, especially those that have differentiated towards a oligodendrocyte phenotype. The administration of function-blocking antibodies via osmotic pumps along with grafted stem cells nearly completely abolished the effect of stem cell grafting, suggesting a minor, but not negligible role for the stem cell-derived glial and neuronal cells in the functional improvement. Similarly, transplantation of NE-GFP-4C stem cells into vitreous body of glaucomatous eyes in rats rescued the retinal ganglion cells otherwise destined to die. The mechanism of action appears to be based upon similar signalling pathways as in the case of injured spinal cord. These data suggest that clonal stem cells exert their effects via multiple mechanisms of action, resulting in considerably improved outcome after a severe experimental CNS injury.