Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures
Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures
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DOI：
10.1073/pnas.1815447116
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发表时间：
2019-01-29
影响因子：
11.1
通讯作者：
Mauck, Robert L.
中科院分区：
文献类型：
--
作者：
Kim, Minwook;Steinberg, David R.;Mauck, Robert L.
最近的一些研究表明，软骨细胞（CH）与骨髓间充质干细胞（MSC）的共培养可以提高其软骨形成。这意味着细胞间通讯决定了受体细胞的命运决定和/或重新编程其代谢状态以支持分化的功能。虽然这种共培养的现象是引人注目的，差异软骨诱导的带状CH MSC共培养物，分子货物的性质，其运输机制仍然不确定。在这里，我们证明，青少年CHs与成人间充质干细胞共培养促进功能分化和改善基质生产。我们进一步证明了两种细胞类型之间的紧密接近是这种反应的先决条件，并且这种相互作用的结果改善了受体MSC的活力，软骨形成，基质形成和体内平衡。此外，我们可视化细胞内内容物从CH转移到附近的MSC，并表明细胞外囊泡（EV）转移的抑制阻断了共培养的协同效应，确定EV作为这些共培养中的主要通信模式。这些发现将促进治疗剂和更有效的递送系统的发展，以促进软骨修复。
Several recent studies have demonstrated that coculture of chondrocytes (CHs) with bone marrow-derived mesenchymal stem cells (MSCs) improves their chondrogenesis. This implies that intercellular communication dictates fate decisions in recipient cells and/or reprograms their metabolic state to support a differentiated function. While this coculture phenomenon is compelling, the differential chondroinductivity of zonal CHs on MSC cocultures, the nature of the molecular cargo, and their transport mechanisms remains undetermined. Here, we demonstrate that juvenile CHs in coculture with adult MSCs promote functional differentiation and improved matrix production. We further demonstrate that close proximity between the two cell types is a prerequisite for this response and that the outcome of this interaction improves viability, chondrogenesis, matrix formation, and homeostasis in the recipient MSCs. Furthermore, we visualized the transfer of intracellular contents from CHs to nearby MSCs and showed that inhibition of extracellular vesicle (EV) transfer blocks the synergistic effect of coculture, identifying EVs as the primary mode of communication in these cocultures. These findings will forward the development of therapeutic agents and more effective delivery systems to promote cartilage repair.