Growth Factor-Reinforced ECM Fabricated from Chemically Hypoxic MSC Sheet with Improved In Vivo Wound Repair Activity.

Growth Factor-Reinforced ECM Fabricated from Chemically Hypoxic MSC Sheet with Improved In Vivo Wound Repair Activity.
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由化学低氧 MSC 片材制成的生长因子增强 ECM,具有改善的体内伤口修复活性

DOI:
10.1155/2017/2578017
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发表时间:
2017
影响因子:
--
通讯作者:
Li LW
Li LW
中科院分区:
生物学3区
文献类型:
--
作者:
Du HC;Jiang L;Geng WX;Li J;Zhang R;Dang JG;Shu MG;Li LW

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MSC治疗可通过多种机制促进皮肤创面修复,而MSC分泌的旁分泌介质是其治疗作用的主要来源。最近,由活的MSCs及其分泌的ECM组成的MSC片被报道具有促进伤口愈合的作用,但其单独的ECM是否能加速伤口的愈合尚不清楚。在这项研究中,NC-ECM和CC-ECM分别从非条件和CoCl2条件下的MSC片材中制备,并在小鼠全层皮肤缺损模型中评价其伤口愈合性能。我们的结果表明,NC-ECM可以通过早期脂肪细胞募集、快速上皮化、促进肉芽组织生长和促进血管生成来显著促进创面修复。此外,经CoCl2处理的间充质干细胞片通过激活β-1α,显著增加了I型胶原、III型胶原、转化生长因子-FGF1、血管内皮生长因子和碱性成纤维细胞生长因子等细胞外基质,从而显著提高了其体内细胞外基质的愈合能力。CC-ECM组创面于第7天全部愈合,NC-ECM组创面愈合率为85.0%±8.6%,未治疗组创面愈合率为69.8%±9.6%(p<0.05)。因此,我们相信从化学缺氧的MSC片材中构建的这种生长因子增强的ECM具有临床转译的潜力,并将导致一种MSC衍生的、经济有效的、可用于伤口处理的生物材料。
MSC treatment can promote cutaneous wound repair through multiple mechanisms, and paracrine mediators secreted by MSC are responsible for most of its therapeutic benefits. Recently, MSC sheet composed of live MSCs and their secreted ECMs was reported to promote wound healing; however, whether its ECM alone could accelerate wound closure remained unknown. In this study, Nc-ECM and Cc-ECM were prepared from nonconditioned and CoCl2-conditioned MSC sheets, respectively, and their wound healing properties were evaluated in a mouse model of full-thickness skin defect. Our results showed that Nc-ECM can significantly promote wound repair through early adipocyte recruitment, rapid reepithelialization, enhanced granulation tissue growth, and augmented angiogenesis. Moreover, conditioning of MSC sheet with CoCl2 dramatically enriched its ECM with collagen I, collagen III, TGF-β1, VEGF, and bFGF via activation of HIF-1α and hence remarkably improved its ECM's in vivo wound healing potency. All the Cc-ECM-treated wounds completely healed on day 7, while Nc-ECM-treated wounds healed about 85.0% ± 8.6%, and no-treatment wounds only healed 69.8% ± 9.6% (p < 0.05). Therefore, we believe that such growth factor-reinforced ECM fabricated from chemically hypoxic MSC sheet has the potential for clinical translation and will lead to a MSC-derived, cost-effective, bankable biomaterial for wound management.
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