Paracrine factors secreted by mesenchymal stem cells (MSCs) have been previously shown to improve cardiac function following acute myocardial infarction (MI). However, cell therapy activates the innate immune response, leading to the rapid elimination of transplanted cells and only short-term therapeutic delivery. Herein, we describe a new strategy to deliver sustained paracrine-mediated MSC therapy to ischemic myocardium. Using an immune evasive, small molecule modified alginate, we encapsulated rat MSC cells in a core–shell hydrogel capsule and implanted them in the pericardial sac of post-MI rats. Encapsulated cells allowed diffusion of reparative paracrine factors at levels similar to non-encapsulated cells in vitro. Encapsulation enabled sustained cell survival with localization over the heart for 2 weeks. The effect of the experimental group on ventricular function and fibrosis was compared with blank (cell free) capsules and unencapsulated MSCs injected into infarcted myocardium. MSC capsules improved post-MI ventricular function ∼2.5× greater than MSC injection. After 4 weeks, post-MI fibrosis was reduced ∼2/3 with MSC capsules, but unchanged with MSC injection. MSC encapsulation with alginate core–shell capsules sustains cell survival and potentiates efficacy of therapy.

中文翻译：

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免疫调节藻酸盐保护间充质干细胞，以将修复因子持续递送至缺血心肌。

间充质干细胞 (MSC) 分泌的旁分泌因子先前已被证明可改善急性心肌梗死 (MI) 后的心脏功能。然而，细胞疗法会激活先天免疫反应，导致移植细胞的快速消除和短期治疗递送。在此，我们描述了一种向缺血心肌提供持续旁分泌介导的 MSC 治疗的新策略。我们使用免疫逃避、小分子修饰的藻酸盐，将大鼠 MSC 细胞封装在核壳水凝胶胶囊中，并将它们植入 MI 后大鼠的心包囊中。包囊细胞允许修复性旁分泌因子在体外以与非包囊细胞相似的水平扩散. 封装使细胞能够在心脏上定位并持续存活 2 周。将实验组对心室功能和纤维化的影响与空白（无细胞）胶囊和注射到梗塞心肌中的未包裹的 MSC 进行比较。MSC 胶囊改善 MI 后心室功能比 MSC 注射大 2.5 倍。4 周后，使用 MSC 胶囊后 MI 后纤维化减少了约 2/3，但使用 MSC 注射后没有变化。用藻酸盐核壳胶囊包裹 MSC 可维持细胞存活并增强治疗效果。