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Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro

机译:单体,多孔II型胶原蛋白支架在体外促进人骨髓间充质干细胞的软骨形成分化

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摘要

Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.
机译:骨关节炎(OA)是疼痛和残疾的常见原因,通常与关节软骨的变性有关。认为已发展为OA的关节表面病变有可能使用组织工程学策略进行修复;然而,指导支架内的细胞分化以产生具有适当的结构,化学和机械性质的组织仍然具有挑战性。我们旨在通过调节支架的组成和物理特性来驱动祖细胞采用软骨生成表型来解决这一问题。在有或没有硫酸软骨素(CS)的情况下,制造避免与纤维状胶原相关的潜在免疫原性的I型和II型单体胶原支架,并评估其刺激人骨髓间充质干细胞软骨分化的能力。免疫组织化学分析显示,细胞在II型支架上产生大量的II型胶原,在I型支架上产生大量的I型胶原。基因表达分析表明,与I型和纯II型支架相比,从支架中快速释放的CS的添加显着上调了II型胶原蛋白的表达。我们得出的结论是,在没有生长因子的情况下,II型胶原蛋白和CS型胶原蛋白可用于促进更具软骨生成性的表型,从而有可能提供预防OA的最终疗法。

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