In vivo differentiation of non-adherent transplanted bone marrow mesenchymal stem cells into neuron-like cells following cerebral ischemia injury in mice / 中国组织工程研究

ABSTRACT

BACKGROUND: Non-adherent mesenchymal stem cells (NA-MSCs) can form colony forming unit of fibroblasts and induce the differentiation into adipocytes, osteoblasts, and chondrocytes.OBJECTIVE: To determine whether non-adherent mesenchymal stem cells (NA-MSCs) in adult mouse bone marrow could differentiate into neuron-like cells in cerebral ischemic region.METHODS: Bilateral femur and tibia of β-Gal transgenic mice was separated, and repeated-transfer was used to collect the fifth-passage purified NA-MSCs which were adjusted at concentration of 1×10~(12)/L Middle cerebral artery occlusion was established in the two groups. After 7 days, 3 μL fifth-passaged NA-MSCs suspension was injected into cerebral ischemic region in the transplantation group, while an equal amount of saline was injected into model group. Survival, distribution, and differentiation of donor cells in cerebral ischemic region were observed at 8 weeks after transplantation.RESULTS AND CONCLUSION: LacZ staining showed that donor cells could express β-Gal protein after 8 weeks and survived in the ischemic region. Simple and double immunohistochemical staining indicated that β-Gal-positive donor cells were detected in necrotic region and at necrotic edge of ischemic model. Additionally, partial cells could express neuro-specific NeuN protein and glial cell-specific GFAP. NA-MSCs are able to survive and migrate in cerebral ischemic region; moreover, partial NA-MSCs can differentiate into mature neuron-like cells or glial cells which participate in repairing brain injury.