Effects of umbilical cord blood neural stem cells via stromal cell-derived factor-1/CXC chemokine receptor 4 signaling on neural recovery in rat models of intracerebral hemorrhage

Abstract

Objective To investigate the effects of umbilical cord blood neural stem cells (UCBNSCs) via stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signaling on neural recovery in rat models of intracerebral hemorrhage. Methods (1) In migration assay in vitro, UCBNSCs were distributed in the upper wells of Transwell plates, and SDF-1 at concentrations of 30, 60 and 120 ng/mL was placed in the lower wells. (2) Sixty rat models of intracerebral hemorrhage were randomly divided into UCBNSCs-transplanted group and phosphate buffer (PBS)-transplanted group (n=30); two d after modeling, 10 L UCBNSCs suspension and same amount of PBS were, respectively, transplanted into the two groups, and intraperitoneal injection of deoxyuridine (BrdU) labeled endogenous neural stem cells was performed; neurological functions were assessed with modified Neurological Severity Scale (mNSS) one d, and one and two weeks after cell transplantation; the expressions of SDF-1, vascular endothelial growth factor (VEGF), glial fibrillar acidic protein (GFAP), and doublecortin (DCX) were detected by immunofluorescence when the rats were sacrificed two weeks after cell transplantation; cell apoptosis was detected by TUNEL. Results (1) In the in vitro experiment, CXCR4 expression could be detected in UCBNSCs; 60 ng/mL SDF-1 had the greatest migration effect on UCBNSCs, and this effect showed statistically significant difference as compared with that at other concentrations (P<0.05). (2) In the in vivo experiment, two weeks after transplantation, the UCBNSCs-transplanted group had significantly increased number of BrdU-labeled cells in the subventricular zone, and significantly larger number of BrdU/DCX and BrdU/GFAP cells than the PBS-transplanted group (P<0.05); the VEGF expression in the brain injury area of the UCBNSCs-transplanted group ([88.30±7.21]/field) was significantly higher than that of PBS-transplanted group ([53.20±4.45]/field, t=4.144, P=0.000); the number of apoptotic cells in the brain injury area of the UCBNSCs-transplanted group ([34.30±2.44]/field) was significantly smaller than that of PBS-transplanted group ([47.70±1.98]/field, t=4.266, P=0.001); two weeks after transplantation, the mNSS scores of UCBNSCs-transplanted group (6.40±0.163) were significantly lower than those of the PBS-transplanted group (7.50±0.17, t=4.714, P=0.002). Conclusion SDF-1/CXCR4 can reach the injured area of cerebral hemorrhage after chemotactic transplantation of UCBNSCs and promote the recovery of nerve function in rats, whose mechanism may be that it can promote neurogenesis and VEGF secretion and inhibit apoptosis. Key words: Umbilical cord blood neural stem cell; Stromal cell-derived factor-1/CXC chemokine receptor 4; Intracerebral hemorrhage; Neurological damage