Current status of neuronal cell xenotransplantation

• Cell therapies may become a viable treatment for neurodegenerative disorders.
• Due to several limitations, human fetal cells are not a viable option.
• Pig-derived neural cells have been studied as an alternative source of neural cells.
• Porcine neural xenografts survive long-term in a primate model of Parkinson's disease.
• Ongoing studies try to improve the strategy to extend neural xenograft survival.

Neural cell transplantation has long been considered as an option for the treatment of neurodegenerative disorders. To date, several patients with Parkinson's and Huntington's diseases have been treated with human fetal-derived neurons with disparate results. However, the limited efficacy to date combined with the scarce availability of human fetal tissues and ethical concerns render this procedure inapplicable to a wide population scale. With a view to overcoming these shortcomings, transplantation of pig-derived cell precursors has been proposed and applied in preclinical and clinical trials. Recently long-term survival (more than 18 months) associated with clinical efficacy has been reported following transplantation of genetically engineered porcine neural precursors in fully immunosuppressed primate recipients. Despite the promising results obtained to date, several questions remain unanswered. In particular, the ideal xenogeneic cell-products to transplant, the extent of the immune response against the implanted xenograft and the most suitable therapeutic strategies to improve engraftment are all issues that still need to be thoroughly addressed. The present review describes the current knowledge in the pig-to-primate xenotransplantation field. In this context, recent data on human-to-nonhuman primate xenogeneic stem cell-based treatments for neurological disorders are discussed.