Small, Volume: 15, Issue: 23, First published: 24 April 2019
间充质干细胞(Mesenchymal stem cells, MSCs)被认为是治疗各种炎症性疾病的有希望的替代方法。然而，骨髓间充质干细胞移植后生存能力差和移植后的移植是骨髓间充质干细胞治疗的主要障碍。生物材料支架被用作载体，通过增加细胞的附着和增殖来增强间充质干细胞的活力和移植。此外，这些支架为移植后的细胞提供了短暂的机械支持。聚乙交脂共丙交脂(PLGA)是一种常见的组织工程聚合物，具有较高的机械强度和良好的生物相容性。然而，由于其疏水性，PLGA支架的细胞粘附能力有限。细胞外基质(ECM)涂层支架为移植后的间充质干细胞提供更好的细胞附着和机械支持。
韩国岭南大学Jee‐Heon Jeong教授用一种新的化合物-多巴胺共轭聚乙烯-丙二酸作为微球制备过程中的稳定剂，对聚乳酸-羟基乙酸(PLGA)微球进行一步ECM功能化的方法。微球表面的多巴胺分子为ECM在水溶液中的结合提供了活性位点。结果表明，当MSCs被ECM功能化的PLGA微球(eMs)包覆后，其生存能力提高。此外，在体外条件下，将一种广谱的半胱天冬酶抑制剂(IDN6556)加入到eMs中可以协同增加MSCs的生存能力。腹腔注射间充质干细胞微球复合物可以通过抑制结肠引流肠系膜淋巴结中CD4+ T细胞的Th1和Th17分化来减轻小鼠模型中的DSS诱导的结肠炎。
Mesenchymal stem cells (MSCs) are considered as a promising alternative to treat various inflammatory diseases. However, poor survival after bone marrow mesenchymal stem cell transplantation and transplantation after transplantation are the main obstacles to bone marrow mesenchymal stem cell therapy. Biomaterial scaffolds are used as carriers to enhance the viability and transplantation of mesenchymal stem cells by increasing cell attachment and proliferation. In addition, these scaffolds provide transient mechanical support for the transplanted cells. Poly (ethylene glycol) (PLGA) is a common tissue engineering polymer with high mechanical strength and good biocompatibility. However, due to its hydrophobicity, the cell adhesion of PLGA scaffold is limited. Extracellular matrix (ECM) coated scaffolds provide better cell attachment and mechanical support for transplanted mesenchymal stem cells.
A new compound, dopamine-conjugated poly vinylmalonic acid, was used as a stabilizer in the preparation of polylactic acid – glycolic acid (PLGA) microspheres by a one-step ECM functionalization method. The dopamine molecule on the surface of the microsphere provides the active site for the binding of ECM in aqueous solution. The results showed that when MSCs were coated by ECM functionalized PLGA microspheres (eMs), their viability was improved. In addition, the addition of a broad-spectrum caspase inhibitor (IDN6556) to eMs can synergically increase the viability of MSCs in vitro. Intraperitoneal injection of mesenchymal stem cell microspheres can alleviate DSS-induced colitis in mouse models by inhibiting Th1 and Th17 differentiation of CD4+ T cells in colon drainage mesenteric lymph nodes. Therefore, the drug-carrying ECM coating surface can be considered as an effective tool to improve the viability, proliferation and function of MSCs after transplantation.