Fabrication of Synthetic Mesenchymal Stem Cells for the Treatment of Acute Myocardial Infarction in Mice.
Fabrication of Synthetic Mesenchymal Stem Cells for the Treatment of Acute Myocardial Infarction in Mice.
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合成间充质干细胞的制备用于治疗小鼠急性心肌梗死
DOI：
10.1161/circresaha.116.310374
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发表时间：
2017-05-26
影响因子：
20.1
通讯作者：
Cheng K
中科院分区：
文献类型：
--
作者：
Luo L;Tang J;Nishi K;Yan C;Dinh PU;Cores J;Kudo T;Zhang J;Li TS;Cheng K
干细胞疗法面临诸多挑战。在将干细胞施用于患者之前，其培养、保存和运输都很困难。干细胞的合成类似物是克服这些障碍的一种新方法，有可能给再生医学带来革命性变化。
我们的目标是制造干细胞的合成类似物，并测试它们对小鼠急性心肌梗死的治疗潜力。
我们将人骨髓间充质干细胞（MSC）分泌的因子包裹在聚乳酸 - 羟基乙酸共聚物（PLGA）微粒中，然后用MSC细胞膜包裹它们。我们将这些治疗性颗粒命名为“合成MSC”（或synMSC）。synMSC呈现出与真正的MSC相似的因子释放特征和表面抗原。synMSC促进了心肌细胞功能，并在体外和体内表现出冷冻保存和冻干稳定性。在急性心肌梗死小鼠模型中，直接注射synMSC促进了血管生成，减轻了左心室重构。
我们成功制造了一种synMSC治疗性颗粒，并证明了它在急性心肌梗死小鼠中的再生潜力。synMSC策略可能为治疗多种疾病的组织工程提供新的见解。
Rationale: Stem cell therapy faces several challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine. Objective: We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice. Methods and Results: We packaged secreted factors from human bone marrow–derived mesenchymal stem cells (MSC) into poly(lactic-co-glycolic acid) microparticles and then coated them with MSC membranes. We named these therapeutic particles synthetic MSC (or synMSC). synMSC exhibited a factor release profile and surface antigens similar to those of genuine MSC. synMSC promoted cardiomyocyte functions and displayed cryopreservation and lyophilization stability in vitro and in vivo. In a mouse model of acute myocardial infarction, direct injection of synMSC promoted angiogenesis and mitigated left ventricle remodeling. Conclusions: We successfully fabricated a synMSC therapeutic particle and demonstrated its regenerative potential in mice with acute myocardial infarction. The synMSC strategy may provide novel insight into tissue engineering for treating multiple diseases.