Neural xenotransplantation: Reconstruction of neuronal circuitry across species barriers

Selective replacement of degenerated neurons in the adult brain with allogeneic fetal neuroblasts is a promising therapeutic modality for human neurodegenerative diseases, but is confounded with practical and potential ethical problems. To evaluate the potential of xenogeneic donors as a cell source for neural transplantation, we have critically examined the available experimental evidence in animal models pertaining to the survival, integration and function of xenogeneic fetal neuroblasts in the host brain. A statistical meta-analysis across multiple studies revealed that immunologically-related transplantation parameters (immunosuppression and donor-host phylogenetic distance) were the main determinants of neural xenograft survival. The immunological basis for xenograft rejection is reviewed in the context of novel immunoprotection strategies designed to enhance xenograft survival. Furthermore, the evidence for behavioral recovery based on anatomical and functional integration of neural xenografts in the host brain is examined with an awareness of developmental considerations. It is concluded that neural xenotransplantation offers a unique opportunity for effective neuronal replacement with significant potential for clinical use.