23-07-08(4:34:39)
Authors:
Subramanian, T., Venkiteswaran, K.
Institutions:
Penn State University Hershey Medical Center
Title of abstract : Human retinal pigment epithelial cell (hRPEC) cotransplants protect mouse fetal ventral mesencephalic striatal xenografts from immune rejection and enhance graft survival
Abstract text:
Striatal xenotranplants require systemic immunosuppression to prevent immune rejection that is associated with significant morbidity. We have previously shown that striatal xenotransplants of hRPEC do not undergo immune rejection up to 18 months and they potentially secrete immunosuppressive substances that provide local immunoprotection. We tested whether hRPEC cotransplants will protect mouse FVM striatal xenotransplants in rats. Identical bilateral striatal transplants were performed in 4 separate groups of rats. Group I rats received hRPE attached to microcarriers (hRPEC-M), Group II rats received FVM, Group III rats received FVM+microcarriers (FVM-M) and Group IV rats received FVM-hRPEC-M . These xenotransplanted non-immunosuppressed rats were euthanized 18 days post-transplantation and examined using immunohistochemistry. Group II and III rats with mouse FVM xenotransplants showed obvious evidence of immune rejection. Group I rats that received hRPEC-M showed accurately placed healthy striatal xenotransplants. All Group IV animals with striatal hRPEC-FVM cotransplants (23/24 targets) appeared healthy with very little or no host immune reaction. Both FVM and hRPEC cotransplants showed morphological and structural integration with the host. Unbiased stereological counts of host OX-42, OX-6 and GFAP positive cells confirmed these findings. Parallel studies with murine microglia demonstrate that hRPEC downregulate pro-inflammatory cytokines, IL-1b and IL-6 expression and actively secrete FAS-L. In addition, hRPEC may provide nutritive or trophic support and neurotransmitter precursors to FVM cotransplants. Cotransplantation with hRPEC may provide a promising new approach to improve neural cell transplant survival and a novel method to avoid long-term side effects of systemic immunosuppression.
