The effect of mesenchymal stem cell shape on the maintenance of multipotency
The effect of mesenchymal stem cell shape on the maintenance of multipotency
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DOI：
10.1016/j.biomaterials.2013.02.029
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发表时间：
2013-05-01
期刊：
影响因子：
14
通讯作者：
Kilian, Kristopher A.
中科院分区：
文献类型：
--
作者：
Zhang, Douglas;Kilian, Kristopher A.
人骨髓间充质干细胞（MSCs）具有分化为多种细胞类型的能力，具有广泛的治疗潜力。然而，当离体培养时，MSC将自发分化，并且已经显示在长时间传代后失去多能性。在体外扩增期间促进多能性维持的细胞培养条件是充分实现MSC的治疗潜力的关键需求。在这里，我们表明，通过将MSC限制在小岛上，我们可以限制不适当的谱系特化，并增强间充质干细胞标志物Stro-1和Endoglin的表达。即使从岛释放和再循环，与在塑料上培养的细胞相比，先前培养的细胞保持更高的MSC标记物表达，同时保持其分化成脂肪细胞和成骨细胞的能力。非图案化细胞暴露于肌球蛋白和Rho相关蛋白激酶（ROCK）的抑制剂导致干细胞标志物的表达增加。我们的研究结果表明，MSC的“干性”的维护需要一个低状态的肌动球蛋白收缩性。这项工作将被证明是有用的培养条件的发展，在体外维持多能间充质干细胞和拟生态位生物材料的设计。(C)2013爱思唯尔有限公司保留所有权利。
Human mesenchymal stem cells (MSCs) have broad therapeutic potential due to their ability to differentiate into multiple cell types. However, when cultured ex vivo MSCs will spontaneously differentiate and have been shown to lose multipotency after prolonged passaging. Cell culture conditions that promote maintenance of multipotency during in vitro expansion are a critical need to fully realize the therapeutic potential of MSCs. Here we show that by confining MSCs to small islands, we can restrict inappropriate lineage specification and enhance the expression of mesenchymal stem cell markers Stro-1 and Endoglin. Even when released from the islands and reseeded, cells previously cultured in patterns maintain higher expression of MSC markers compared to cells cultured on plastic, while maintaining their ability to differentiate into adipocytes and osteoblasts. Exposure of non-patterned cells to inhibitors of myosin and Rho-associated protein kinase (ROCK) leads to increased expression of stem cell markers. Our findings suggest that maintenance of MSC "sternness" requires a low state of actomyosin contractility. This work will prove useful in the development of culture conditions for the maintenance of multipotent MSCs in vitro and for the design of niche-mimetic biomaterials. (C) 2013 Elsevier Ltd. All rights reserved.