Neural xenotransplantation: the fate of human umbilical cord blood neural stem cells (HUCB-NSC) and host response to brain injury and cell grafi

Neural stem cells (NSC) are potentially a promising treatment strategy for neurological diseases. There is a proof that intracerebral grafting of NSC can have restorative effects. Nevertheless, a major obstacle is the induction of a host-derived immune response followed by graft injection. The goal of the study was to analyze the fate of HUCB-NSC transplanted in injured rat brain. Methods: 2×104 HUCB-NSC were tx into corpus callosum of a focal brain injury induced by OUA injection (1 μl/50 nmol) into striatum of adult Wistar rats. After 1, 3, 7 and 14 days brains were removed and analyzed immunocytochemically. Results. One day after HUCB tx, most cells remained in the injection site with few cells migrated to the lesion area. Concomitantly, infi ltration of ED1+ and CD15+ cells with occasional appearance of CD5+ and CD45+ cells was seen. At 3rd day some HUCB-NSC in graft core expressed neuronal (NF-200) or astrocytic (GFAP) markers. Migration of tx cells into the lesion was observed. At 7th day HUCB-NSC were found close to injured area. By 14 days, no viable HUCB-NSC have been noticed with cellular debris in graft core. Limited number of ED1+, CD15+, CD5+ and CD45+ cells were found most likely due to HUCB-NSC rejection. Conclusions. Massive loss of transplanted HUCB-NSC was probably due to post traumatic infl ammation and acute immune reaction of the host in term of cross-species grafting paradigm. Supported by MSHE grant N401 014235 and Fondation Jerome Lejeune scientifi c grant.