Our previous studies reported that urine-derived stem cells (USCs) possess a strong self-renewal ability and multidirectional differentiation potential and thus are an ideal candidate cell source for hepatocellular transplantation. USC transplantation may repair the pathological changes of chronic liver injury to a certain extent, and hypoxia pretreatment may improve the recovery efficiency of USCs. Therefore, the present study aimed to investigate the possible mechanism of the improved recovery efficiency of hypoxia-pretreated USCs. A chronic liver injury model was established by intraperitoneal injection of carbon tetrachloride into nude mice. USCs were transplanted via caudal vein injection. Hematoxylin and eosin staining and Masson's staining were performed to determine the pathology of the liver. Immunofluorescence and frozen section biopsy were performed to determine differentiation and cell fusion in vivo. Cell coculture was used to detect cell fusion in vitro. The proliferative ability of USCs was evaluated using cell viability and colony formation assays, and the migratory functions of USCs were evaluated using wound healing and transwell assays. The degeneration of hepatocytes and the level of fibrosis in the hypoxia transplantation group were improved compared with the normoxia transplantation group. It was found that exogenous USCs may be differentiated into functional hepatocytes or fused with hepatocytes in vivo. C-X-C motif chemokine (CXC) ligand 12 (CXCL12) expression levels in liver tissue of the chronic liver injury model were upregulated compared with those in the control group. The expression of CXC receptor 4 (CXCR4) in hypoxia-pretreated USCs was also significantly upregulated. The results suggested that USCs fused with different types of liver cells and that hypoxia treatment promoted the fusion rate in vitro by upregulating CXCR4 signaling. Furthermore, hypoxia pretreatment promoted cell proliferation, migration, and cell fusion by inducing CXCR4 signaling, leading to USC-elicited liver tissue recovery following injury in vivo.

中文翻译：

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缺氧预处理通过上调CXCR4促进慢性损伤小鼠肝脏中人尿干细胞的增殖和迁移


我们前期的研究表明，尿源干细胞（USCs）具有很强的自我更新能力和多向分化潜力，是肝细胞移植的理想候选细胞来源。 USC移植可在一定程度上修复慢性肝损伤的病理改变，缺氧预处理可提高USC的恢复效率。因此，本研究旨在探讨缺氧预处理的USCs恢复效率提高的可能机制。采用四氯化碳腹腔注射裸鼠建立慢性肝损伤模型。通过尾静脉注射移植 USC。进行苏木精和伊红染色以及马森染色以确定肝脏的病理学。进行免疫荧光和冰冻切片活检以确定体内分化和细胞融合。细胞共培养用于体外检测细胞融合。使用细胞活力和集落形成测定评估 USC 的增殖能力，并使用伤口愈合和 Transwell 测定评估 USC 的迁移功能。缺氧移植组肝细胞变性和纤维化水平较常氧移植组有所改善。研究发现，外源性USCs可能在体内分化为功能性肝细胞或与肝细胞融合。慢性肝损伤模型肝组织中CXC基序趋化因子（CXC）配体12（CXCL12）表达水平较对照组上调。缺氧预处理的 USC 中 CXC 受体 4 ( CXCR4 ) 的表达也显着上调。 结果表明，USCs 与不同类型的肝细胞融合，缺氧处理通过上调CXCR4信号传导促进体外融合率。此外，缺氧预处理通过诱导CXCR4信号传导促进细胞增殖、迁移和细胞融合，从而导致 USC 诱导的体内损伤后肝组织恢复。