Applicability of regenerative oligodendrocyte precursor cell optic nerve transplantation in rat model of demyelinating disease.

Abstract

Cell-based therapies, particularly transplanted human oligodendrocyte progenitor cells (OPCs), are being explored for neuroprotection and remyelination in demyelinating diseases of the central nervous system (CNS). In this study, we investigated the potential of OPC transplantation into the optic nerve of dark agouti (DA) rats with experimental autoimmune encephalomyelitis (EAE). Human OPCs were transplanted 30 days after EAE induction in one optic nerve, while the contralateral nerve was injected with a vehicle. FTY720 (fingolimod) was administered starting from day 25 post-EAE to prevent graft rejection. Rats were monitored clinically and electrophysiologically using visually evoked potentials (VEPs) for up to 90 days post-transplant. Histological analysis of OPC viability, myelin, and axonal integrity was performed on days 30, 60, and 90 post-transplant. At days 30 and 60, sparse OPCs were detected in the injected optic nerve. However, no live cells were detected on day 90. There were no significant differences in myelin or axonal integrity between the OPC- and vehicle-injected nerves. The VEP traces were severely distorted throughout the 90-day follow-up. This approach did not show long-term viability following direct injection of OPCs in the optic nerve of EAE rats. Challenges related to graft rejection and cell transplantation are discussed, with implications for future research in cell-based therapies.