Conditioned media from endothelial progenitor cells cultured in simulated microgravity promote angiogenesis and bone fracture healing.
Conditioned media from endothelial progenitor cells cultured in simulated microgravity promote angiogenesis and bone fracture healing.
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DOI：
10.1186/s13287-020-02074-y
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发表时间：
2021-01-08
影响因子：
7.5
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Kong L;Wang Y;Wang H;Pan Q;Zuo R;Bai S;Zhang X;Lee WY;Kang Q;Li G
内皮祖细胞 (EPC) 的旁分泌信号有利于血管生成，从而促进组织再生。微重力（MG）环境被发现可以促进各种干细胞或祖细胞的功能潜力。本研究旨在阐明 MG 对 EPC 条件培养基 (CM) 的促血管生成特性和骨折修复能力的影响。人外周血来源的 EPC 在 MG 或正常重力 (NG) 下培养，然后分析血管生成基因表达。此外，收集了MG（MG-CM）或NG（NG-CM）下的无血清CM，并在人脐静脉内皮细胞（HUVEC）中检查了它们的促血管生成特性。为了研究MG-CM对骨折愈合的影响，将其注射到大鼠模型的骨折间隙中，并进行放射线摄影、组织学和力学测试，以评估新生血管形成和骨折愈合结果。 MG上调缺氧诱导因子1α（HIF-1α）和内皮一氧化氮合酶（eNOS）的表达并促进NO释放。与NG-CM相比，MG-CM通过NO诱导FAK/Erk1/2-MAPK信号通路的激活显着促进HUVEC的增殖、迁移和血管生成。此外，MG-CM在大鼠胫骨骨折模型中被证实能够改善骨折区域的血管生成活性，加速骨折愈合，并能很好地恢复骨折骨的生物力学性能，优于NG-CM。这些发现为我们深入了解使用 MG 生物反应器通过 HIF-1α/eNOS/NO 轴增强 EPC 旁分泌信号的血管生成特性，并且 MG-CM 的给药有利于骨折修复。在线版本包含可在 10.1186/s13287-020-02074-y 获取的补充材料。
Paracrine signaling from endothelial progenitor cells (EPCs) is beneficial for angiogenesis and thus promotes tissue regeneration. Microgravity (MG) environment is found to facilitate the functional potentials of various stem or progenitor cells. The present study aimed to elucidate the effects of MG on pro-angiogenic properties and fracture repair capacities of conditioned media (CM) from EPCs. Human peripheral blood-derived EPCs were cultured under MG or normal gravity (NG) followed by analysis for angiogenic gene expression. Furthermore, the serum-free CM under MG (MG-CM) or NG (NG-CM) were collected, and their pro-angiogenic properties were examined in human umbilical vein endothelial cells (HUVECs). In order to investigate the effects of MG-CM on fracture healing, they were injected into the fracture gaps of rat models, and radiography, histology, and mechanical test were performed to evaluate neovascularization and fracture healing outcomes. MG upregulated the expression of hypoxia-induced factor-1α (HIF-1α) and endothelial nitric oxide synthase (eNOS) and promoted NO release. Comparing to NG-CM, MG-CM significantly facilitated the proliferation, migration, and angiogenesis of HUVECs through NO-induced activation of FAK/Erk1/2-MAPK signaling pathway. In addition, MG-CM were verified to improve angiogenic activities in fracture area in a rat tibial fracture model, accelerate fracture healing, and well restore the biomechanical properties of fracture bone superior to NG-CM. These findings provided insight into the use of MG bioreactor to enhance the angiogenic properties of EPCs’ paracrine signals via HIF-1α/eNOS/NO axis, and the administration of MG-CM favored bone fracture repair. The online version contains supplementary material available at 10.1186/s13287-020-02074-y.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
9.8
作者：
Filipowska J;Tomaszewski KA;Niedźwiedzki Ł;Walocha JA;Niedźwiedzki T
通讯作者：
Niedźwiedzki T
影响因子：
8.3
作者：
Lee CZ;Xue Z;Hao Q;Yang GY;Young WL
通讯作者：
Young WL
影响因子：
1.2
作者：
Emontzpohl, Christoph;Simons, David;Stoppe, Christian
通讯作者：
Stoppe, Christian
内皮祖细胞分泌的外泌体通过刺激血管生成加速牵引成骨过程中的骨再生
影响因子：
7.5
作者：
Jia, Yachao;Zhu, Yu;Chai, Yimin
通讯作者：
Chai, Yimin