Influence of decellularized matrix derived from human mesenchymal stem cells on their proliferation, migration and multi-lineage differentiation potential

Influence of decellularized matrix derived from human mesenchymal stem cells on their proliferation, migration and multi-lineage differentiation potential
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DOI:
10.1016/j.biomaterials.2012.03.012
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发表时间:
2012-06-01
期刊:
影响因子:
14
通讯作者:
Tuan, Rocky S.
Tuan, Rocky S.
中科院分区:
工程技术1区
文献类型:
--
作者:
Lin, Hang;Yang, Guang;Tuan, Rocky S.

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开发促进干细胞增殖和分化的生物材料是组织工程和再生的关键要求。间充质干细胞(mesenchymal stem cells,MSCs)来源的细胞外基质(Extracellular matrix,ECM)能够维持MSCs在体外扩增培养过程中的分化潜能,并能恢复衰老MSCs的活性,这表明MSC ECM(MECM)可能是一种合适的培养基质,可用于增强MSCs生物材料支架的生物活性。本研究旨在表征MECM对MSC影响的生物学性质和特异性。在尿素中提取由人MSC体外产生的天然ECM,并且用胃蛋白酶消化进一步处理残余沉淀(分别表示为U-MECM和HP-MECM)。然后将MECM产品作为基质涂覆在标准组织培养塑料上,并研究了接种在涂覆表面上的MSC的行为。我们的结果显示,U-MECM涂层显著加速MSC增殖、附着、扩散、迁移和多谱系分化(即,骨生成和脂肪生成)。非胶原蛋白可能是U-MECM中的生物活性组分,因为在I型胶原和HP-MECM上培养的MSC显示出相似的生物活性,并且基于SDS-PAGE,I型胶原似乎是HP-MECM中保留的主要蛋白组分。这些发现支持了MECM在生物材料支架制剂中的生物学效用,以增强MSC生物活性,包括增殖、迁移和多谱系分化,用于组织再生应用。(C)2012爱思唯尔有限公司版权所有。
Developing biomaterials to promote stem cell proliferation and differentiation is a critical requirement in tissue engineering and regeneration. Extracellular matrix (ECM) derived from mesenchymal stem cells (MSCs) has recently been shown to be able to maintain the differentiation potential of MSCs during culture expansion and to restore the activities of aging MSCs, suggesting that MSC ECM (MECM) may be a suitable culture substrate to enhance the bioactivity of biomaterial scaffolds for MSCs. This investigation aims to characterize the biological nature and specificity of the influence of the MECM on MSCs. Native ECM produced by human MSC in vitro was extracted in urea, and the residual pellet was further processed with pepsin digestion (denoted as U-MECM and HP-MECM, respectively). The MECM products were then coated as a substrate on standard tissue culture plastic, and the behavior of MSCs seeded on the coated surfaces was studied. Our results showed that U-MECM coating dramatically accelerated MSC proliferation, attachment, spread, migration and multi-lineage differentiation (i.e., osteogenesis and adipogenesis), compared to collagen type I and HP-MECM coating. Non-collagenous proteins are likely the bioactive components in U-MECM, as MSCs cultured on collagen type I and HP-MECM showed similar biological activities, and collagen type I appeared to be the major protein components remaining in HP-MECM based on SDS-PAGE. These findings support the biological utility of MECM in the formulation of biomaterial scaffolds to enhance MSC bioactivities, including proliferation, migration and multi-lineage differentiation, for tissue regeneration applications. (C) 2012 Elsevier Ltd. All rights reserved.