Inhibition of osteogenic differentiation of human mesenchymal stem cells
Inhibition of osteogenic differentiation of human mesenchymal stem cells
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DOI：
10.1111/j.1524-475x.2007.00244.x
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发表时间：
2007-05-01
影响因子：
2.9
通讯作者：
Mao, Jeremy J.
中科院分区：
文献类型：
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作者：
Moioli, Eduardo K.;Hong, Liu;Mao, Jeremy J.
间充质干细胞（hMSC）已被证明可以分化为成骨细胞，而成骨细胞又能够形成类似于骨的组织。本研究旨在研究 hMSC 对成骨的抑制作用。骨髓来源的 hMSC 在分化为成骨细胞期间或之后，用不同剂量的转化生长因子 β-3 (TGF β 3) 进行处理。 TGF beta 3 被封装在聚（DL-乳酸-乙醇酸）（PLGA）微球中，并通过在 hMSC 和 hMSC 衍生的成骨细胞的成骨培养物中受控递送释放长达 28 天。 TGFβ3 的受控释放抑制了 hMSC 的成骨分化，碱性磷酸酶活性和染色显着降低以及矿物质沉积减少就证明了这一点。 hMSCs分化为成骨细胞后，TGFβ3的控制释放不仅进一步抑制碱性磷酸酶和矿物质沉积，而且还抑制骨钙素表达。这些发现证明了通过控制生长因子的释放来持续调节干细胞和/或干细胞衍生的谱系特异性细胞的行为的潜力。间充质干细胞成骨分化的减弱不仅有助于理解发育过程中成骨的调节和模式，而且有助于理解骨硬化、颅缝早闭和心脏瓣膜钙化等多种病理模型。
Mesenchymal stem cells (hMSCs) have been shown to differentiate into osteoblasts that, in turn, are capable of forming tissues analogous to bone. The present study was designed to investigate the inhibition of osteogenesis by hMSCs. Bone marrow-derived hMSCs were treated with transforming growth factor beta-3 (TGF beta 3) at various doses during or after their differentiation into osteogenic cells. TGF beta 3 was encapsulated in poly(DL-lactic-co-glycolic acid) (PLGA) microspheres and released via controlled delivery in the osteogenic culture of hMSCs and hMSC-derived osteoblasts for up to 28 days. Controlled release of TGF beta 3 inhibited the osteogenic differentiation of hMSCs, as evidenced by significantly reduced alkaline phosphatase activity and staining, as well as decreased mineral deposition. After hMSCs had been differentiated into osteoblasts, controlled release of TGF beta 3 further inhibited not only alkaline phosphatase and mineral deposition but also osteocalcin expression. These findings demonstrate the potential for sustained modulation of the behavior of stem cells and/or stem cell-derived lineage-specific cells via controlled release of growth factor(s). The attenuation of osteogenic differentiation of MSCs may facilitate understanding not only the regulation and patterning of osteogenesis in development but also several pathological models such as osteopetrosis, craniosynostosis, and heart valve calcification.