Endogenous Extracellular Matrices Enhance Human Mesenchymal Stem Cell Aggregate Formation and Survival
Endogenous Extracellular Matrices Enhance Human Mesenchymal Stem Cell Aggregate Formation and Survival
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DOI：
10.1002/btpr.1686
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发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Ma, Teng
中科院分区：
文献类型：
--
作者：
Kim, Junho;Ma, Teng
人间充质干细胞或基质细胞（hMSC）疗法在广泛的疾病中具有前景。然而，低效率的细胞递送和损伤部位的低细胞存活降低了疗效，并且是基于hMSC的治疗的主要障碍。已经发现三维（3D）hMSC聚集体的形成通过增强治疗因子的分泌来激活hMSC功能，以改善细胞迁移和存活。作为骨髓基质细胞，hMSC是细胞外基质（extracellular matrix，ECM）蛋白和生长因子的重要来源，它们通过旁分泌和自分泌作用形成相互作用的微环境，影响hMSC的命运。然而，迄今为止，细胞外微环境对聚集体中hMSC性质的影响仍然未知。在本研究中，我们研究了内源性ECM基质对hMSC聚集体形成和缺血应激下存活的作用。结果表明，与酶促分离的hMSCs（称为EDA）形成的聚集体相反，通过热提升（称为TLAs）形成的聚集体中的内源性ECM的保存增强了细胞增殖，多谱系潜力和缺血应激下的存活。TLA中改善的细胞增殖和活力归因于TLA中内源性ECM蛋白的掺入及其促有丝分裂和抗氧化性质。结果证明了一种通过热响应表面形成hMSC聚集体的新方法，并强调了ECM在保留3D聚集体中hMSC特性方面的显着贡献。(c)2013年美国化学工程师学会生物技术。程序：29：441451，2013
Human mesenchymal stem or stromal cell (hMSC) therapies have promise across a wide range of diseases. However, inefficient cell delivery and low cell survival at injury sites reduce efficacy and are the major barriers in hMSC-based therapy. Formation of three-dimensional (3D) hMSC aggregates has been found to activate hMSC functions from enhancing secretion of therapeutic factors for improving cell migration and survival. As the stromal cells in bone marrow, hMSCs are significant sources of extracellular matrix (ECM) proteins and growth factors, which form an interactive microenvironment to influence hMSC fate via paracrine and autocrine actions. To date, however, the impact of the extracellular microenvironment on hMSC properties in the aggregates remains unknown. In the present study, we investigated the role of endogenous ECM matrices on hMSC aggregate formation and survival under ischemic stress. The results demonstrated that the preservation of endogenous ECM in the aggregates formed by thermal lifting (termed TLAs) as opposed to the aggregates formed by enzymatically detached hMSCs (termed EDAs) enhanced cell proliferation, multilineage potential, and survival under ischemic stress. The improved cell proliferation and viability in the TLAs is attributed to the incorporation of endogenous ECM proteins in the TLAs and their promitotic and antioxidant properties. The results demonstrate a novel method for the formation of hMSC aggregates via thermal responsive surface and highlight the significant contribution of the ECM in preserving hMSC properties in the 3D aggregates. (c) 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 441451, 2013