To optimize the regenerative proficiency of stem cells, a cardiopoietic protein‐based cocktail consisting of multiple growth factors has been developed and advanced into clinical trials for treatment of ischemic heart failure. Streamlining the inductors of cardiopoiesis would address the resource intensive nature of the current stem cell enhancement protocol. To this end, the microencapsulated‐modified‐mRNA (M³RNA) technique was here applied to introduce early cardiogenic genes into human adipose‐derived mesenchymal stem cells (AMSCs). A single mesodermal transcription factor, Brachyury, was sufficient to trigger high expression of cardiopoietic markers, Nkx2.5 and Mef2c. Engineered cardiopoietic stem cells (eCP) featured a transcriptome profile distinct from pre‐engineered AMSCs. In vitro, eCP demonstrated protective antioxidant capacity with enhanced superoxide dismutase expression and activity; a vasculogenic secretome driving angiogenic tube formation; and macrophage polarizing immunomodulatory properties. In vivo, in a murine model of myocardial infarction, intramyocardial delivery of eCP (600 000 cells per heart) improved cardiac performance and protected against decompensated heart failure. Thus, heart repair competent stem cells, armed with antioxidant, vasculogenic, and immunomodulatory traits, are here engineered through a protein‐independent single gene manipulation, expanding the available regenerative toolkit.

中文翻译：

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Brachyury 工程师心脏修复感受态干细胞

为了优化干细胞的再生能力，一种由多种生长因子组成的基于心脏生成蛋白的混合物已被开发出来，并已进入临床试验以治疗缺血性心力衰竭。简化心脏生成的感应器将解决当前干细胞增强方案的资源密集型问题。为此，微囊化修饰的 mRNA（M ³RNA）技术被用于将早期心源性基因引入人类脂肪间充质干细胞（AMSCs）。单个中胚层转录因子 Brachyury 足以触发心脏生成标志物 Nkx2.5 和 Mef2c 的高表达。工程心脏生成干细胞 (eCP) 具有不同于预制 AMSCs 的转录组特征。在体外，eCP 表现出保护性抗氧化能力，增强了超氧化物歧化酶的表达和活性；驱动血管生成管形成的血管生成分泌组；和巨噬细胞极化免疫调节特性。在体内，在心肌梗塞的小鼠模型中，eCP 的心肌内递送（每个心脏 600 000 个细胞）改善了心脏功能并防止失代偿性心力衰竭。因此，心脏修复能力强的干细胞，