Matrix-mediated retention of adipogenic differentiation potential by human adult bone marrow-derived mesenchymal stem cells during ex vivo expansion

Matrix-mediated retention of adipogenic differentiation potential by human adult bone marrow-derived mesenchymal stem cells during ex vivo expansion
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DOI:
10.1016/j.biomaterials.2005.03.024
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发表时间:
2005-11-01
期刊:
影响因子:
14
通讯作者:
Kaplan, DL
Kaplan, DL
中科院分区:
工程技术1区
文献类型:
--
作者:
Mauney, JR;Volloch, V;Kaplan, DL

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最近,已经开发了利用脂肪形成祖细胞用于脂肪组织工程的基于细胞的方法,并且据报道在促进体内脂肪形成和修复缺损部位方面取得了成功。对于自体应用,人骨髓来源的间充质干细胞(MSC)已被建议作为脂肪组织工程应用的潜在细胞来源,这是由于它们能够从成人骨髓抽吸物中分离和离体扩增以及它们多能分化成各种间充质谱系(包括脂肪形成)的多功能性。由于骨髓中存在的MSC的频率相对较低,这些细胞的广泛离体扩增对于获得用于组织工程策略的治疗性细胞群是必要的。目前,由于在常规组织培养塑料(TCP)基质上进行广泛的离体扩增后其成脂分化潜能的衰减,MSC用于脂肪组织工程的利用受到限制。在本研究中,检查了变性I型胶原(DC)基质在体外扩增过程中保持MSC成脂潜力的能力。与早期相比,在体外检测了脂肪细胞相关标志物和功能,以响应脂肪形成培养条件21天。传代MSC和晚期传代MSC在TCP上离体扩增。结果表明,在DC基质上离体扩增的晚期传代MSC表达成脂标志物(脂肪酸结合蛋白-4、脂蛋白脂肪酶、酰基辅酶A合成酶、脂蛋白酶、促进性葡萄糖转运蛋白-4和脂质积累)的能力与早期传代细胞相似,并且与在TCP上扩增的晚期传代MSC相反,具有显著的保留。DC基质在广泛的离体扩增后保留脂肪细胞相关标志物和MSC功能的能力代表了一种新的培养技术,以扩增用于组织工程应用的功能性成脂祖细胞。(c)2005年由Elsevier Ltd.出版
Recently, cell-based approaches utilizing adipogenic progenitor cells for fat tissue engineering have been developed and reported to have success in promoting in vivo adipogenesis and the repair of defect,sites. For autologous applications, human bone marrow-derived mesenchymal stem cells (MSCs) have been suggested as a potential cell source for adipose tissue engineering applications due to their ability to be isolated and ex vivo expanded from adult bone marrow aspirates and their versatility for pluripotent differentiation into various mesenchymal lineages including adipogenic. Due to the relatively low frequency of MSCs present within bone marrow, extensive ex vivo expansion of these cells is necessary to obtain therapeutic cell populations for tissue engineering strategies. Currently, utilization of MSCs for adipose tissue engineering is limited due to the attenuation of their adipogenic differentiation potential following extensive ex vivo expansion on conventional tissue culture plastic (TCP) substrates. In the present study, the ability of a denatured collagen type I (DC) matrix to preserve MSC adipogenic potential during ex vivo expansion was examined. Adipocyte-related markers and functions were examined in vitro in response to adipogenic culture conditions for 21 days in comparison to early.. passage MSCs and late passage MSCs ex vivo expanded on TCP. The results demonstrated significant preservation of the ability of late passage MSCs ex vivo expanded on the DC matrix to express adipogenic markers (fatty acid-binding protein-4, lipoprotein lipase, acyl-CoA synthetase, adipsin, facilitative glucose transporter-4, and accumulation of lipids) similar to the early passage cells and in contrast to late passage MSCs expanded on TCP. The ability of the DC matrix to preserve adipocyte-related markers and functions of MSCs following extensive ex vivo expansion represents a novel culture technique to expand functional adipogenic progenitors for tissue engineering applications. (c) 2005 Published by Elsevier Ltd.