NEURAL XENOTRANSPLANTATION - RECONSTRUCTION OF NEURONAL CIRCUITRY ACROSS SPECIES BARRIERS

Selective replacement of degenerated neurons in the adult brain with a llogeneic fetal neuroblasts is a promising therapeutic modality for hu man neurodegenerative diseases, but is confounded with practical and p otential ethical problems. To evaluate the potential of xenogeneic don ors as a cell source for neural transplantation, we have critically ex amined the available experimental evidence in animal models pertaining to the survival, integration and function of xenogeneic fetal neurobl asts in the host brain. A statistical meta-analysis across multiple st udies revealed that immunologically-related transplantation parameters (immunosuppression and donor-host phylogenetic distance) were the mai n determinants of neural xenograft survival. The immunological basis f or xenograft rejection is reviewed in the context of novel immunoprote ction strategies designed to enhance xenograft survival. Furthermore, the evidence for behavioral recovery based on anatomical and functiona l integration of neural xenografts in the host brain is examined with an awareness of developmental considerations. It is concluded that neu ral xenotransplantation offers a unique opportunity for effective neur onal replacement with significant potential for clinical use.