Moioli Eduardo K, Hong Liu, Mao Jeremy J
Department of Biomedical Engineering, College of Dental Medicine, Columbia University, Fu Foundation School of Engineering and Applied Sciences, New York, New York 10032, USA.
Wound Repair Regen. 2007 May-Jun;15(3):413-21. doi: 10.1111/j.1524-475X.2007.00244.x.
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 (TGFbeta3) at various doses during or after their differentiation into osteogenic cells. TGFbeta3 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 TGFbeta3 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 TGFbeta3 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.
间充质干细胞（hMSCs）已被证明可分化为成骨细胞，而成骨细胞又能够形成类似于骨的组织。本研究旨在调查hMSCs对成骨作用的抑制情况。在骨髓来源的hMSCs分化为成骨细胞的过程中或之后，用不同剂量的转化生长因子β-3（TGFβ3）对其进行处理。TGFβ3被包裹在聚（DL-乳酸-乙醇酸）（PLGA）微球中，并在hMSCs和成骨细胞来源的成骨细胞培养物中通过控释方式释放长达28天。TGFβ3的控释抑制了hMSCs的成骨分化，这表现为碱性磷酸酶活性和染色显著降低以及矿物质沉积减少。在hMSCs分化为成骨细胞后，TGFβ3的控释不仅进一步抑制了碱性磷酸酶和矿物质沉积，还抑制了骨钙素的表达。这些发现表明，通过生长因子的控释，有可能持续调节干细胞和/或干细胞来源的谱系特异性细胞的行为。MSCs成骨分化的减弱可能不仅有助于理解发育过程中成骨的调节和模式形成，还有助于理解几种病理模型，如骨质石化、颅缝早闭和心脏瓣膜钙化。
