The efficacy of stem cell therapy for ischemia repair has been limited by low cell retention rate. Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β super family, which has multiple effects on development, physiology and diseases. The objective of the study is to investigate whether GDF11 could affect the efficacy of stem cell transplantation. We explored the effects of GDF11 on proangiogenic activities of mesenchymal stem cells (MSCs) for angiogenic therapy in vitro and in vivo. Mouse bone marrow-derived MSCs were transduced with lentiviral vector to overexpress GDF11 (MSCGDF11). After exposed to hypoxia and serum deprivation for 48 h, MSCGDF11 were significantly better in viability than control MSCs (MSCvector). MSCGDF11 also had higher mobility and better angiogenic paracrine effects. The cytokine antibody array showed more angiogenic cytokines in the conditioned medium of MSCGDF11 than that of MSCvector, such as epidermal growth factor, platelet-derived growth factor-BB, placenta growth factor. When MSCs (1 × 106 cells in 50 μl) were injected into ischemic hindlimb of mice after femoral artery ligation, MSCGDF11 had higher retention rate in the muscle than control MSCs. Injection of MSCGDF11 resulted in better blood reperfusion and limb salvage than that of control MSCs after 14 days. Significantly more CD31+ endothelial cells and α-SMA + smooth muscle cells were detected in the ischemic muscles that received MSCGDF11. The effects of GDF11 were through activating TGF-β receptor and PI3K/Akt signaling pathway. Our study demonstrated an essential role of GDF11 in promoting therapeutic functions of MSCs for ischemic diseases by enhancing MSC viability, mobility, and angiogenic paracrine functions.

中文翻译：

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GDF11 增强间充质干细胞对血管生成的治疗功能

干细胞治疗缺血修复的功效受到低细胞保留率的限制。生长分化因子 11 (GDF11) 是转化生长因子-β 超家族的成员，对发育、生理和疾病具有多重作用。该研究的目的是调查 GDF11 是否会影响干细胞移植的疗效。我们探讨了 GDF11 对用于体外和体内血管生成治疗的间充质干细胞 (MSC) 促血管生成活性的影响。用慢病毒载体转导小鼠骨髓来源的 MSCs 以过表达 GDF11 (MSCGDF11)。在缺氧和血清剥夺 48 小时后，MSCGDF11 的活力明显优于对照 MSCs (MSCvector)。MSCGDF11 还具有更高的流动性和更好的血管生成旁分泌作用。细胞因子抗体阵列显示MSCGDF11条件培养基中的血管生成细胞因子比MSCvector更多，如表皮生长因子、血小板衍生生长因子-BB、胎盘生长因子。当将 MSCs（1×106 个细胞，50 μl）注射到小鼠股动脉结扎后的缺血后肢时，MSCGDF11 在肌肉中的保留率高于对照 MSCs。注射 MSCGDF11 在 14 天后导致比对照 MSCs 更好的血液再灌注和肢体挽救。在接受 MSCGDF11 的缺血肌肉中检测到明显更多的 CD31+ 内皮细胞和 α-SMA+ 平滑肌细胞。GDF11的作用是通过激活TGF-β受体和PI3K/Akt信号通路。