Photo-crosslinked gelatin-hyaluronic acid methacrylate hydrogel-committed nucleus pulposus-like differentiation of adipose stromal cells for intervertebral disc repair

Photo-crosslinked gelatin-hyaluronic acid methacrylate hydrogel-committed nucleus pulposus-like differentiation of adipose stromal cells for intervertebral disc repair
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光交联明胶-透明质酸甲基丙烯酸酯水凝胶定向髓核样脂肪基质细胞分化用于椎间盘修复

DOI:
10.1002/term.2841
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发表时间:
2019-04-01
影响因子:
3.3
通讯作者:
Fan, Shunwu
Fan, Shunwu
中科院分区:
工程技术3区
文献类型:
--
作者:
Chen, Pengfei;Ning, Lei;Fan, Shunwu

文献摘要

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髓核样分化一直是干细胞应用于椎间盘修复的挑战。可注射生物材料和干细胞的结合可能会解决这个问题,因为跨膜力可以通过整合素影响细胞内环境。在这项研究中,我们开发了一种光交联明胶-透明质酸甲基丙烯酸酯(GelHA)水凝胶的策略,使脂肪基质细胞(ASC)进行髓核样分化,用于椎间盘修复。在 GelHA 水凝胶中分离并培养 ASC,以评估髓核样分化。用中和抗体研究整合素v6的功能。在大鼠椎间盘退变模型中研究了 ASC 与 GelHA 水凝胶对椎间盘修复的功效。结果表明,GelHA水凝胶促进ASCs向髓核样分化,而整合素v6中和抗体在体外阻止ASCs表达髓核基质。 GelHA水凝胶和ASC的结合促进了具有更多髓核基质和显着更高椎间盘高度指数的大鼠的椎间盘修复质量。研究结果表明,光交联的 GelHA 水凝胶和 ASC 的结合可以使 ASC 向髓核样分化,并提高 ASC 椎间盘修复的功效。这些发现提出了一种有前途的基于干细胞的椎间盘修复策略。
Nucleus pulposus-like differentiation is always the challenge with application of stem cells for intervertebral disc repair. The combination of injectable biomaterials and stem cells may provide a resolution for this problem, as the transmembrane force can affect the intracellular environment through integrin . In this study, we developed a strategy of photo-crosslinked gelatin-hyaluronic acid methacrylate (GelHA) hydrogel to commit the nucleus pulposus-like differentiation of adipose stromal cells (ASCs) for intervertebral disc repair. ASCs were isolated and cultured in GelHA hydrogel to evaluate nucleus pulposus-like differentiation. The function of integrin v6 was investigated with neutralising antibody. The efficacy of ASCs with GelHA hydrogel for intervertebral disc repair was studied in a rat model of intervertebral disc degeneration. The results showed that GelHA hydrogel promoted ASCs nucleus pulposus-like differentiation and that integrin v6 neutralising antibody prevented ASCs from expression of nucleus pulposus matrix in vitro. The combination of GelHA hydrogel and ASCs promoted quality intervertebral disc repair in rats with much more nucleus pulposus matrix and significantly higher disc height index. The findings have demonstrated that the combination of photo-crosslinked GelHA hydrogel and ASCs can commit ASCs to nucleus pulposus-like differentiation and improve the efficacy of ASCs for intervertebral disc repair. These findings suggest a promising stem cell-based strategy for intervertebral disc repair.