Concise Review: Innate and Adaptive Immune Recognition of Allogeneic and Xenogeneic Cell Transplants in the Central Nervous System

Over the last 30 years, numerous allogeneic and xenogeneic cell grafts have been transplanted into the central nervous system (CNS) of mice and men in an attempt to cure neurological diseases. In the early studies, human or porcine embryonic neural cells were grafted in the striatum of animals or patients in an attempt to replace lost neurons. Although the immune-privileged status of the brain as a recipient organ was widely accepted, it rapidly became evident that CNS-grafted allogeneic and xenogeneic cells could be recognized and rejected by the immune system, resulting in poor neural graft survival and limited functional recovery. Since then, the CNS transplantation field has witnessed a sharp rise in the number of studies in which allogeneic and xenogeneic neural or mesenchymal stem cells (NSCs or MSCs, respectively) are transplanted, predominantly aiming at providing trophic stimulation and promoting endogenous repair of the brain. Interestingly, in many recent NSC and MSC-based publications functional improvement was used as the principal measure to evaluate the success of cell transplantation, while the fate of transplanted cells remained largely unreported. In this review, we first attempt to understand why primary neural cell isolates were largely substituted for NSCs and MSCs in cell grafting studies. Next, we review the current knowledge on the immune mechanisms involved in the recognition and rejection of allogeneic and xenogeneic cellular grafts in the CNS. Finally, we propose strategies to reduce graft immunogenicity and to improve graft survival in order to design improved cell-based CNS therapies. Stem Cells Translational Medicine 2017;6:1434-1441.