A collagen-glycosaminoglycan scaffold supports adult rat mesenchymal stem cell differentiation along osteogenic and chondrogenic routes

A collagen-glycosaminoglycan scaffold supports adult rat mesenchymal stem cell differentiation along osteogenic and chondrogenic routes
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DOI:
10.1089/ten.2006.12.459
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发表时间:
2006-03-01
期刊:
影响因子:
--
通讯作者:
Campbell, VA
Campbell, VA
中科院分区:
生物2区
文献类型:
--
作者:
Farrell, E;O'Brien, FJ;Campbell, VA

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成体间充质干细胞具有沿多种谱系分化的倾向,产生新的骨、软骨、肌肉或脂肪。胶原蛋白是骨的一种正常成分,提供强度和结构稳定性,因此是一种潜在的候选物,可以作为基质,在其上从各自的间充质来源的前体中改造骨和软骨。在这项研究中,胶原-糖胺聚糖支架为培养成年大鼠间充质干细胞提供了一个合适的三维(3-D)环境,并诱导其沿成骨和软骨谱系分化。结果表明,成年大鼠间充质干细胞在胶原-糖胺聚糖支架上生长并受到成骨因子(地塞米松、抗坏血酸、β -甘油磷酸酯)的刺激时可以发生成骨,通过骨特异性蛋白、胶原I和骨钙素的时间诱导以及随后的基质矿化来评估。成骨因子与细胞外调节蛋白激酶(ERK)的激活相耦合,该激酶被发现在成骨过程中发挥作用。除了支持成骨外,当细胞种子支架暴露于成软骨因子(地塞米松和TGF-1 β)时,胶原II免疫反应性增加,这表明支架还可以提供支持软骨形成的合适三维环境。
Adult mesenchymal stem cells have the proclivity to differentiate along multiple lineages giving rise to new bone, cartilage, muscle, or fat. Collagen, a normal constituent of bone, provides strength and structural stability and is therefore a potential candidate for use as a substrate on which to engineer bone and cartilage from their respective mesenchymal-derived precursors. In this study, a collagen-glycosaminoglycan scaffold was used to provide a suitable three-dimensional (3-D) environment on which to culture adult rat mesenchymal stem cells and induce differentiation along the osteogenic and chondrogenic lineages. The results demonstrate that adult rat mesenchymal stem cells can undergo osteogenesis when grown on the collagen-glycosaminoglycan scaffold and stimulated with osteogenic factors ( dexamethasone, ascorbic acid, beta-glycerophosphate), as evaluated by the temporal induction of the bone-specific proteins, collagen I and osteocalcin, and subsequent matrix mineralization. The osteogenic factors were coupled to activation of the extracellular-regulated protein kinase (ERK), and this kinase was found to play a role in the osteogenic process. As well as supporting osteogenesis, when the cell-seeded scaffold was exposed to chondrogenic factors ( dexamethasone and TGF-1 beta), collagen II immunoreactivity was increased, providing evidence that the scaffold can also provide a suitable 3-D environment that supports chondrogenesis.