Transplantation of human amniotic mesenchymal stem cells promotes neurological recovery in an intracerebral hemorrhage rat model

Abstract

Objective We assessed whether transplantation of human amniotic mesenchymal stem cells (hAMSCs) promotes neurological recovery in an intracerebral hemorrhage rat model. In addition, the potential mechanisms underlying the possible benefits of this therapy were investigated. Methods A total of 138 male Wistar rats were divided into fibroblasts group, phosphate-buffered saline(PBS) group and hAMSCs group (n=46). The intracerebral hemorrhage (ICH) models were induced by intrastriatal injection of VII collagenase and then intracerebrally administered hAMSCs, Fibroblasts, or PBS at 24 h after ICH. hAMSCs were characterized using flow cytometry. Immunohistochemistry were performed to assay differentiation, angiogenesis and neurogenesis. The expressions of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were analyzed by ELISA. Neurological function was assessed with the modified neurological severity score (mNSS). Results hAMSCs displayed a fibroblast-like morphology, were positive for CD29, CD44, CD90, CD105, and CD166, and negative for CD19, CD34, and CD45. From 7 d after ICH, mNSS scores of the hAMSCs group were significantly higher than that of PBS group and Fibroblasts group (P<0.05). Fourteen days after ICH, the number of Brdu+ cells in the hAMSCs group (55.33±6.59) was significantly higher than that in PBS group (25.50±2.90) and Fibroblasts group (26.66±3.58) (P<0.05). The number of Brdu+/DCX+ cells (30.66±3.65) in the hAMSCs group was significantly higher than that in PBS group (10.00±2.54) and fibroblasts group (11.83±2.70) (P<0.05). The number of von Willebrand factor (vWF+) blood vessels [(67.50±6.76)/mm2] in the hAMSCs group was significantly higher than that in PBS group [(28.83±5.58)/mm2] and Fibroblasts group [(31.66±6.33)/mm2] (P<0.05). Seven and fourteen days after ICH, the levels of BDNF[(63.16±2.31) pg/mg, (38.57±3.69) pg/mg] of the hAMSCs group were significantly higher than that of PBS group [(43.18±2.30) pg/mg, (18.28±2.39) pg/mg] and Fibroblasts group[(46.18±2.45) pg/mg, (20.52±2.81) pg/mg](P<0.05). Seven, fourteen and twenty-one days after ICH, the levels of VEGF [(43.32±3.65) pg/mg, (30.90±2.62) pg/mg, (24.89±2.85) pg/mg] of the hAMSCs group were significantly higher than that of PBS group [(20.81±3.06) pg/mg, (14.44±2.32) pg/mg, (11.42±1.48) pg/mg] and Fibroblasts group [(22.88±2.62) pg/mg, (15.41±2.40) pg/mg, (10.57±1.54) pg/mg]. The transplanted hAMSCs survived for at least 27 d and were negative for fi-tubulin Ⅲ and glial fibrillary acidic protein. Conclusion hAMSCs treatment significantly promotes neurological recovery in rats after ICH. The mechanism of action could be mediated by increasing neurotrophic factor expression, and promotion of neurogenesis and angiogenesis. Thus, hAMSCs are candidate stem cells for the treatment of ICH. Key words: Mesenchymal stem cells; Human amniotic; Intracerebral hemorrhage; Transplantation; Neurological recovery