College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.
Department of Medical Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.
Small. 2019 Jun;15(23):e1901269. doi: 10.1002/smll.201901269. Epub 2019 Apr 24.
Mesenchymal stem cells (MSCs) are considered as a promising alternative for the treatment of various inflammatory disorders. However, poor viability and engraftment of MSCs after transplantation are major hurdles in mesenchymal stem cell therapy. Extracellular matrix (ECM)-coated scaffolds provide better cell attachment and mechanical support for MSCs after transplantation. A single-step method for ECM functionalization on poly(lactic-co-glycolic acid) (PLGA) microspheres using a novel compound, dopamine-conjugated poly(ethylene-alt-maleic acid), as a stabilizer during the preparation of microspheres is reported. The dopamine molecules on the surface of microspheres provide active sites for the conjugation of ECM in an aqueous solution. The results reveal that the viability of MSCs improves when they are coated over the ECM-functionalized PLGA microspheres (eMs). In addition, the incorporation of a broad-spectrum caspase inhibitor (IDN6556) into the eMs synergistically increases the viability of MSCs under in vitro conditions. Intraperitoneal injection of the MSC-microsphere hybrid alleviates experimental colitis in a murine model via inhibiting Th1 and Th17 differentiation of CD4 T cells in colon-draining mesenteric lymph nodes. Therefore, drug-loaded ECM-coated surfaces may be considered as attractive tools for improving viability, proliferation, and functionality of MSCs following transplantation.
间充质干细胞（MSCs）被认为是治疗各种炎症性疾病的一种很有前途的替代方法。然而，MSCs 移植后的存活率和植入率低是间充质干细胞治疗的主要障碍。细胞外基质（ECM）涂层支架为 MSCs 移植后提供了更好的细胞附着和机械支持。本文报道了一种在聚（乳酸-共-乙醇酸）（PLGA）微球的制备过程中使用一种新型化合物多巴胺偶联聚（乙烯-共-马来酸）作为稳定剂，对其进行 ECM 功能化的一步法。微球表面的多巴胺分子为 ECM 在水溶液中的共轭提供了活性位点。结果表明，当 MSCs 被涂覆在 ECM 功能化的 PLGA 微球（eMs）上时，其存活率提高。此外，将广谱半胱天冬酶抑制剂（IDN6556）掺入 eMs 中，可协同提高 MSC 在体外条件下的存活率。MSC-微球杂交体的腹腔注射通过抑制结肠引流肠系膜淋巴结中 CD4 T 细胞的 Th1 和 Th17 分化，缓解了实验性结肠炎小鼠模型中的疾病。因此，载药 ECM 涂层表面可以被认为是改善 MSCs 移植后存活率、增殖和功能的有吸引力的工具。
