CCR2 improves homing and engraftment of adipose-derived stem cells in dystrophic mice
CCR2 improves homing and engraftment of adipose-derived stem cells in dystrophic mice
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CCR2 改善营养不良小鼠脂肪干细胞的归巢和植入
DOI：
10.1186/s13287-020-020
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Zhang Cheng
中科院分区：
文献类型：
--
作者：
Wang Liang;Li Huan;Lin Jinfu;He Ruojie;Chen Menglong;Zhang Yu;Liao Ziyu;Zhang Cheng
背景：肌营养不良症是一种由肌营养不良蛋白缺乏引起的常见神经肌肉疾病，目前缺乏有效的治疗方法。脂肪源性干细胞（ADSC）的系统移植是一种有前途的治疗方法，但其低疗效仍然是一个挑战。趋化因子系统介导的干细胞归巢在系统移植中发挥着关键作用。在这里，我们研究了特定趋化因子受体的过度表达是否可以改善营养不良小鼠中 ADSC 全身移植的肌肉归巢和治疗效果...方法：我们分析了基因表达综合数据库的多个微阵列数据集，以确定候选趋化因子受体，然后评估营养不良小鼠不同组织和器官中靶配体的蛋白质表达。使用慢病毒系统在小鼠 ADSC 中过表达候选趋化因子受体，将其全身移植到营养不良小鼠中，然后评估运动功能、干细胞肌肉归巢、肌营养不良蛋白表达和肌肉病理学...结果：趋化因子谱分析确定 C-C 趋化因子受体 (CCR)2 是改善 ADSC 归巢的潜在靶点。我们发现其配体C-C趋化因子配体（CCL）2和CCL7在营养不良小鼠肌肉中的水平高于其他组织和器官。此外，CCR2 过表达提高了 ADSC 的迁移能力并保持了其多谱系分化潜力。与对照 ADSC 相比，过表达 CCR2 的 ADSC 移植显示出更好的肌肉归巢，并进一步改善了营养不良小鼠的运动功能、肌营养不良蛋白表达和肌肉病理学……结论：这些结果表明，CCR2 改善了营养不良小鼠全身移植后的 ADSC 肌肉归巢和治疗效果。
Background: Dystrophinopathy, a common neuromuscular disorder caused by the absence of dystrophin, currently lacks effective treatments. Systemic transplantation of adipose-derived stem cells (ADSCs) is a promising treatment approach, but its low efficacy remains a challenge. Chemokine system-mediated stem cell homing plays a critical role in systemic transplantation. Here, we investigated whether overexpression of a specific chemokine receptor could improve muscle homing and therapeutic effects of ADSC systemic transplantation in dystrophic mice...Methods: We analysed multiple microarray datasets from the Gene Expression Omnibus to identify a candidate chemokine receptor and then evaluated the protein expression of target ligands in different tissues and organs of dystrophic mice. The candidate chemokine receptor was overexpressed using the lentiviral system in mouse ADSCs, which were used for systemic transplantation into the dystrophic mice, followed by evaluation of motor function, stem cell muscle homing, dystrophin expression, and muscle pathology...Results: Chemokine-profile analysis identified C-C chemokine receptor (CCR)2 as the potential target for improving ADSC homing. We found that the levels of its ligands C-C chemokine ligand (CCL)2 and CCL7 were higher in muscles than in other tissues and organs of dystrophic mice. Additionally, CCR2 overexpression improved ADSC migration ability and maintained their multilineage-differentiation potentials. Compared with control ADSCs, transplantation of those overexpressing CCR2 displayed better muscle homing and further improved motor function, dystrophin expression, and muscle pathology in dystrophic mice...Conclusions: These results demonstrated that CCR2 improved ADSC muscle homing and therapeutic effects following systemic transplantation in dystrophic mice.