Stem cell‐based therapy has great potential in regenerative medicine. However, the survival and engraftment rates of transplanted stem cells in disease regions are poor and limit the effectiveness of cell therapy due to the fragility of stem cells. Here, an approach involving a single‐cell coating of surface‐anchored nanogel to regulate stem cell fate with anti‐apoptosis capacity in the hypoxic and ischemic environment of infarcted hearts is developed for the first time. A polysialic acid‐based system is used to anchor microbial transglutaminase to the external surface of the cell membrane, where it catalyzes the crosslinking of gelatin. The single‐cell coating with surface‐anchored nanogel endows mesenchymal stem cells (MSCs) with stress resistance by blocking the activity of apoptotic cytokines including the binding of tumor necrosis factor α (TNFα) to tumor necrosis factor receptor, which in turn maintains mitochondrial integrity, function and protects MSCs from TNFα‐induces apoptosis. The administration of surface engineered MSCs to hearts results in significant improvements in engraftment, cardiac function, infarct size, and vascularity compared with using uncoated MSCs in treating myocardial infarction. The surface‐anchored, biocompatible cell surface engineering with nanogel armor provides a new way to produce robust therapeutic stem cells and may explore immense potentials in cell‐based therapy.

中文翻译：

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表面锚定纳米凝胶涂层通过降低细胞因子受体结合途径赋予干细胞抗应激能力和修复能力

干细胞疗法在再生医学领域具有巨大潜力。然而，移植干细胞在疾病区域的存活率和植入率较差，并且由于干细胞的脆弱性限制了细胞治疗的有效性。在这里，首次开发了一种涉及表面锚定纳米凝胶的单细胞涂层的方法，以在梗塞心脏的缺氧和缺血环境中调节具有抗凋亡能力的干细胞命运。基于聚唾液酸的系统用于将微生物转谷氨酰胺酶锚定到细胞膜的外表面，在那里催化明胶的交联。表面锚定纳米凝胶的单细胞涂层通过阻断凋亡细胞因子的活性，包括肿瘤坏死因子α（TNFα）与肿瘤坏死因子受体的结合，赋予间充质干细胞（MSC）抗应激能力，从而维持线粒体完整性、发挥作用并保护 MSC 免受 TNF α的影响 - 诱导细胞凋亡。与使用未包被的 MSC 治疗心肌梗塞相比，将表面工程化的 MSC 注入心脏可显着改善植入、心脏功能、梗塞面积和血管分布。具有纳米凝胶装甲的表面锚定、生物相容性细胞表面工程提供了一种生产强大的治疗性干细胞的新方法，并可能探索基于细胞的治疗的巨大潜力。