Fate of transplanted adult neural stem/progenitor cells and bone marrow-derived mesenchymal stromal cells in the injured adult rat spinal cord and impact on functional recovery

Background: Neural stem/progenitor cells derived from the ependymal region of the spinal cord may have the ability to regenerate the injured mammalian spinal cord as they do in some lower vertebrates. It has also been suggested that BMSCs provide an environment conducive to regeneration in the injured cord. Methods: In the current Study, both spinal cord-derived NSPCs and BMSCs were cultured from adult male rats expressing eGFP. Neurospheres or dissociated BMSCs were transplanted 9 days after clip compression injury (35-g force). Cell survival and fate, and functional recovery were examined after 14 weeks. Results: BMSCs showed no neural differentiation but had much better survival than NSPCs. Transplanted NSPCs differentiated mainly into astrocytes (14.7%) and oligodendrocytes (34.7%), but no neurons. No functional improvement was seen in either transplant group. However, in the NSPC group there was a significant inverse correlation between the functional scores and the number of transplanted astrocytes. A separate experiment to test the effect of cyclosporine on survival and fate of transplanted NSPCs showed' that high-dose (20 mg/kg per day) cyclosporine improved cell survival, but had no effect on cell fate. Conclusions: Further work is required before these transplantation strategies can be recommended for patients. These results are promising in that we have found potentially beneficial mechanisms of action of the transplanted cells including differentiation of many NSPCs into oligodendrocytes with the possibility of promoting remyelination, and potential axonal guidance through guiding strands of matrix generated by the BMSCs. (C) 2008 Elsevier Inc. All rights reserved.