Analysis of the neurogenic potential of human umbilical cord blood neural stem cells (HUCB-NSC) after their transplantation into rat brain

Transplantation (tx) of neural stem cells (NSC) is the key strategy of cell replacement therapy in the central nervous system. The goal of the study was to compare survival, migration and differentiation of HUCB-NSC after their tx into the brain of neonatal and adult Wistar rats. Methods: HUCB-NSC (2 x 10 super(4)) labeled with CMFDA were tx into SVZ of the postnatal day 0 (P0) rats or into intact brain of adult rats. After 1, 3, 7, 14 or 21 days brains were removed, frozen and cut into 20 um coronary slices, then inxmunohistochemical studies were performed to visualize HUCB-NSC fate in the brain. Results: In neonatal rats, 3 days after tx most of HUCB-NSC remained in the graft. During the first week HUCB-NSC started to disperse and migrate. HUCB-NSC situated at the periphery of the graft or in mi-gratory stream display proliferation marker (Ki67). After 7-21 days HUCB-NSC survived in the host brain with many cells expressing neuronal or astrocytic phenotypes. Few of HUCB-NSC presented the features of adult neurons (MAP2+ with long protrusions). In adult rats, 3 days after tx, HUCB-NSC form dense deposit with single cells migrating into brain tissue. Most of the HUCB-NSCs stayed undifferentiated with few cells expressing neuronal (NF200) or astrocytic (GFAP) markers. After 7 days numerous HUCB-NSC situated inside the graft underwent degeneration and subsequent depletion. Tx HUCB-NSC induced inflammatory response detected by macrophage/microglia (ED1+) accumulation and astrogliosis (GFAP+). No viable HUCB-NSC were found after 14 days. Conclusions: Host environment dictates the fate of tx neural stem cells derived from human cord blood however immunological response in adult rats limits the time of observation due to short survival of HUCB-NSC.