The transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) can promote hypoxic-ischemic brain damage (HIBD) nerve repair, but finding suitable seed cells to optimize transplantation and improve treatment efficiency is an urgent problem to be solved. In this study, we induced hUC-MSCs into dedifferentiated hUC-MSCs (De-hUC-MSCs), and the morphology, stem cell surface markers, proliferation and tri-directional differentiation ability of the De-hUC-MSCs and hUC-MSCs were detected. A whole-gene chip was utilized for genome cluster, gene ontology and KEGG pathway analyses of differentially expressed genes. De-hUC-MSCs were transplanted into HIBD rats, and behavioral experiments and immunofluorescence assays were used to assess the therapeutic effect. A lentivirus vector for human stromal cell-derived factor-1 (hSDF-1α) was constructed, and the role of hSDF-1α in the neuroprotective effect and mechanism of De-hUC-MSCs was verified. De-hUC-MSCs displayed similar cell morphology, stem cell surface marker expression, cell proliferation and even three-dimensional differentiation ability as hUC-MSCs but exhibited greater treatment potential in vivo. The reprogramming mechanism of hSDF-1α participated in the dedifferentiation process. By successfully constructing a stable hSDF-1α cell line, we found that De-hUC-MSCs might participate in nerve repair through the hSDF-1α/CXCR4/PI3K/Akt pathway. De-hUC-MSCs reprogramming of endogenous hSDF-1α expression may mediate the hSDF-1α/CXCR4/PI3K/Akt pathway involved in nerve repair in HIBD rats.

人脐带间充质干细胞（hUC-MSCs）移植可以促进缺氧缺血性脑损伤（HIBD）神经修复，但寻找合适的种子细胞来优化移植并提高治疗效率是亟待解决的问题。本研究将hUC-MSCs诱导为去分化hUC-MSCs（De-hUC-MSCs），并对De-hUC-MSCs和hUC-MSCs的形态、干细胞表面标志物、增殖及三向分化能力进行了研究。检测到。利用全基因芯片对差异表达基因进行基因组聚类、基因本体和KEGG通路分析。将De-hUC-MSCs移植到HIBD大鼠体内，通过行为实验和免疫荧光检测来评估治疗效果。构建人基质细胞衍生因子1（hSDF-1α）慢病毒载体，验证hSDF-1α对De-hUC-MSCs的神经保护作用及机制。De-hUC-MSCs表现出与hUC-MSCs相似的细胞形态、干细胞表面标志物表达、细胞增殖甚至三维分化能力，但在体内表现出更大的治疗潜力。hSDF-1α的重编程机制参与了去分化过程。通过成功构建稳定的hSDF-1α细胞系，我们发现De-hUC-MSCs可能通过hSDF-1α/CXCR4/PI3K/Akt通路参与神经修复。内源性 hSDF-1α 表达的去 hUC-MSC 重编程可能介导参与 HIBD 大鼠神经修复的 hSDF-1α/CXCR4/PI3K/Akt 通路。