Institute of Cardiovascular Disease, The Affiliated Changzhou Second People's Hospital of Nanjing Medical Universityō, Changzhou, 213003 Jiangsu, China; Department of Cardiology, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, 213003 Jiangsu, China.
Institute of Cardiovascular Disease, The Affiliated Changzhou Second People's Hospital of Nanjing Medical Universityō, Changzhou, 213003 Jiangsu, China; Dalian Medical University, Dalian, 116000 Liaoning, China.
Biomed Pharmacother. 2023 May;161:114557. doi: 10.1016/j.biopha.2023.114557. Epub 2023 Mar 22.
Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs), due to their inner functional substances, have shown great value in treating acute myocardial infarction (AMI). However, their clinical application is limited by a low yield. In the present study, we cultured EVs using a hollow fiber bioreactor-based three-dimensional (3D) system, and assessed their therapeutic effectiveness on AMI.
The MSCs separated from fresh human umbilical cord were planted into the flasks of two systems: two-dimensional (2D) culture and hollow-fiber-bioreactor based 3D culture. EVs were extracted from the culture supernatants. Characteristics and yields of EVs from two culture systems, namely 2D-EVs and 3D-EVs, were compared. A rat model of AMI was built up to assess their therapeutic efficacy on AMI.
The yield of 3D-EVs was higher, with biofunctions similar to those of 2D-EVs. 3D-EVs repressed the apoptosis of cardiomyocytes, facilitated angiogenesis, and regulated the transition of macrophage subpopulations after myocardial infarction, and eventually improved cardiac function in the AMI rats.
The hollow fiber 3D culture system can increase the yield of MSCs-derived EVs to render a strong cardioprotective effect in AMI rats.
间充质干细胞（MSCs）来源的细胞外囊泡（EVs）因其内含的功能性物质，在治疗急性心肌梗死（AMI）方面显示出巨大的价值。然而，由于产量低，其临床应用受到限制。在本研究中，我们使用基于中空纤维生物反应器的三维（3D）系统培养 EVs，并评估其在 AMI 中的治疗效果。
从新鲜人脐带中分离出的 MSCs 种植到两个系统的培养瓶中：二维（2D）培养和基于中空纤维生物反应器的 3D 培养。从培养上清液中提取 EVs。比较两种培养系统（2D-EVs 和 3D-EVs）的 EVs 的特征和产量。建立大鼠 AMI 模型，评估其对 AMI 的治疗效果。
3D-EVs 的产量较高，具有与 2D-EVs 相似的生物功能。3D-EVs 抑制心肌细胞凋亡，促进血管生成，并调节心肌梗死后巨噬细胞亚群的转化，最终改善 AMI 大鼠的心脏功能。
中空纤维 3D 培养系统可以提高 MSCs 来源的 EVs 的产量，在 AMI 大鼠中产生强大的心脏保护作用。
