Transplantation of mesenchymal stromal cells (MSCs) is an emerging therapy for the treatment of heart failure. However, the delivery method of MSC is currently suboptimal. The use of self-assembling peptide hydrogels, including PuraMatrix^® (PM; 3-D Matrix, Ltd), has been reported for clinical hemostasis and in research models. This study demonstrates the feasibility and efficacy of an advanced approach for MSC-therapy, that is coating of the epicardium with the instantly-produced PM hydrogel incorporating MSCs (epicardial PM-MSC therapy). We optimized the conditions/procedure to produce “instant” PM-MSC complexes. After spreading on the epicardium by easy pipetting, the PM-MSC complex promptly and stably adhere to the beating heart. Of note, this treatment achieved more extensive improvement of cardiac function, with greater initial retention and survival of donor MSCs, compared to intramyocardial MSC injection in rat heart failure models. This enhanced efficacy was underpinned by amplified myocardial upregulation of a group of tissue repair-related genes, which led to enhanced repair of the damaged myocardium, i.e. augmented microvascular formation and reduced interstitial fibrosis. These data suggest a potential for epicardial PM-MSC therapy to be a widely-adopted treatment of heart failure. This approach may also be useful for treating diseases in other organs than the heart.

中文翻译：

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自组装肽水凝胶能够用间充质基质细胞即时涂覆心脏外膜，用于治疗心力衰竭


间充质基质细胞（MSC）移植是治疗心力衰竭的新兴疗法。然而，MSC 的递送方法目前并不理想。据报道，自组装肽水凝胶（包括 PuraMatrix ^® （PM；3-D Matrix, Ltd））可用于临床止血和研究模型。这项研究证明了一种先进的 MSC 治疗方法的可行性和有效性，即用立即生产的含有 MSC 的 PM 水凝胶涂覆心外膜（心外膜 PM-MSC 疗法）。我们优化了生产“即时”PM-MSC 复合物的条件/程序。通过简单的移液器将PM-MSC复合物铺展在心外膜上后，PM-MSC复合物迅速稳定地粘附在跳动的心脏上。值得注意的是，与大鼠心力衰竭模型中心肌内注射 MSC 相比，这种治疗实现了心脏功能更广泛的改善，供体 MSC 的初始保留和存活率更高。这种功效的增强是由一组组织修复相关基因的心肌上调放大所支撑的，这导致受损心肌的修复增强，即增强微血管形成并减少间质纤维化。这些数据表明心外膜 PM-MSC 疗法有可能成为广泛采用的心力衰竭治疗方法。这种方法也可用于治疗心脏以外的其他器官的疾病。