Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Clinical Research Institute, Daejeon St. Mary's Hospital, college of medicine, The Catholic University of Korea, Daejeon 37661, Republic of Korea.
J Control Release. 2020 May 10;321:602-615. doi: 10.1016/j.jconrel.2020.02.047. Epub 2020 Mar 17.
Myocardial infarction (MI) causes serious loss of cardiac muscle and dysfunction. To restore MI, exogenous stem cells should be efficiently delivered. However, due to severe physical and physiological cardiac environment, recent strategies have faced challenges, including low cell persistence, low integration, and delayed therapeutic effects. Herein, we proposed mesenchymal stem cell (MSC) therapeutic platform using adhesive protein-based immiscible condensed liquid system (APICLS) derived from bioengineered mussel adhesive protein (MAP). With high encapsulation efficiency and survival rate of encapsulated MSCs, APICLS was successfully grafted by intramyocardial injection and distributed throughout the scarred myocardium. Its underwater adhesiveness and biocompatibility fostered integration with damaged tissue, resulting in high cell persistence and maximized paracrine effects. Bioactive molecules released from APICLS with MSCs induced angiogenesis and cardioprotection, delayed cardiac remodeling, reduced fibrosis, and recovered contractive force. Thus, our proposed strategy represents an innovative approach for recovering infarcted cardiac tissues with damaged structural and contractive function.
心肌梗死(MI)会导致严重的心肌损失和功能障碍。为了修复 MI,需要有效地输送外源性干细胞。然而,由于严重的物理和生理心脏环境,最近的策略面临挑战,包括细胞持续时间短、整合率低和治疗效果延迟。在此,我们提出了一种基于黏附蛋白的不混溶凝聚液相分离系统(APICLS)的间充质干细胞(MSC)治疗平台,该系统源自工程化贻贝类黏附蛋白(MAP)。所制备的 MSC 包封体具有高包封效率和存活率,可通过心肌内注射成功接枝,并分布于整个瘢痕心肌中。其水下黏附性和生物相容性促进了与受损组织的整合,从而提高了细胞的持续时间和最大限度的旁分泌作用。APICLS 与 MSC 共同释放的生物活性分子可诱导血管生成和心脏保护,延迟心脏重构,减少纤维化,并恢复收缩力。因此,我们提出的策略为恢复具有受损结构和收缩功能的梗死心脏组织提供了一种创新方法。