Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem Cells
Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem Cells
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DOI：
10.1155/2019/5654324
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发表时间：
2019-01-01
影响因子：
4.3
通讯作者：
Ma, Zhen
中科院分区：
文献类型：
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作者：
Winston, Tackla S.;Suddhapas, Kantaphon;Ma, Zhen
干细胞技术和 3D 生物制造方法的结合提供了与体内组织的生理相似性以及修复和再生受损人体组织的能力。间充质干细胞（MSC）因其免疫抑制特性和多能潜力而被广泛用于再生医学应用。为了在无需患者捐赠和侵入性操作的情况下获得大量高质量的 MSC，我们使用仅补充一种生长因子 (bFGF) 和两种小分子（SB431542 和 CHIR99021）的无血清 E6 培养基将 MSC 与人诱导多能干细胞 (hiPSC-MSC) 区分开来。分化的细胞表现出常见 MSC 特异性表面标志物（CD90、CD73、CD105、CD106、CD146 和 CD166）的高表达，并且具有高效的成骨和软骨分化能力。借助这些细胞，我们能够在普朗尼克涂层的可重复使用的 PDMS 设备中制造具有高一致性和稳健性的 MSC 组织环。根据内径和外环直径对 MSC 组织环进行表征，并观察到细胞-基质相互作用诱导的细胞类型依赖性组织收缩。我们的简化 hiPSC-MSC 分化、模块化制造程序和无血清培养条件的方法对于可扩展制造用于不同再生医学应用的 MSC 组织环具有巨大潜力。
Combination of stem cell technology and 3D biofabrication approaches provides physiological similarity to in vivo tissues and the capability of repairing and regenerating damaged human tissues. Mesenchymal stem cells (MSCs) have been widely used for regenerative medicine applications because of their immunosuppressive properties and multipotent potentials. To obtain large amount of high-quality MSCs without patient donation and invasive procedures, we differentiated MSCs from human-induced pluripotent stem cells (hiPSC-MSCs) using serum-free E6 media supplemented with only one growth factor (bFGF) and two small molecules (SB431542 and CHIR99021). The differentiated cells showed a high expression of common MSC-specific surface markers (CD90, CD73, CD105, CD106, CD146, and CD166) and a high potency for osteogenic and chondrogenic differentiation. With these cells, we have been able to manufacture MSC tissue rings with high consistency and robustness in pluronic-coated reusable PDMS devices. The MSC tissue rings were characterized based on inner diameter and outer ring diameter and observed cell-type-dependent tissue contraction induced by cell-matrix interaction. Our approach of simplified hiPSC-MSC differentiation, modular fabrication procedure, and serum-free culture conditions has a great potential for scalable manufacturing of MSC tissue rings for different regenerative medicine applications.