Research paperCyclosporine-immunosuppression does not affect survival of transplanted skin-derived precursor Schwann cells in the injured rat spinal cord

- Skin-derived precursor Schwann cells were grafted into rats with SCI.
- The effect of immune rejection on cell grafts was explored.
- Immunosuppression did not impact cell graft survival.
- Mismatching strain of donor and recipient did not affect survival.
- Immune rejection is not a key limiting factor in graft survival.

A major goal of Schwann cell (SC) transplantation for spinal cord injury (SCI) is to fill the injury site to create a bridge for regenerating axons. However, transplantation of peripheral nerve SCs requires an invasive biopsy, which may result in nerve damage and donor site morbidity. SCs derived from multipotent stem cells found in skin dermis (SKP-SCs) are a promising alternative. Regardless of source, loss of grafted SCs post-grafting is an issue in studies of regeneration, with survival rates ranging from ∼1 to 20% after ≥6 weeks in rodent models of SCI. Immune rejection has been implicated in these low survival rates. Therefore, our aim was to explore the role of the immune response on grafted SKP-SC survival in Fischer rats with a spinal hemisection injury. We compared SKP-SC survival 6 weeks post-transplantation in: (I) cyclosporine-immunosuppressed rats (n = 8), (II) immunocompetent rats (n = 9), and (III) rats of a different sub-strain than the SKP-SC donor rats (n = 7). SKP-SC survival was similar in all groups, suggesting immune rejection was not a main factor in SKP-SC loss observed in this study. SKP-SCs were consistently found on laminin expressed at the injury site, indicating detachment-mediated apoptosis (i.e., anoikis) might play a major role in grafted cell loss.