Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xi'an, Shaanxi 710069, China.
Department of Plastic and Burn Surgery, Tangdu Hospital, Forth Military Medical University, Xi'an, Shaanxi 710038, China.
Biomed Res Int. 2017;2017:2578017. doi: 10.1155/2017/2578017. Epub 2017 Sep 5.
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 CoCl-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 CoCl dramatically enriched its ECM with collagen I, collagen III, TGF-1, VEGF, and bFGF via activation of HIF-1 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% ( < 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.
MSC 治疗可通过多种机制促进皮肤伤口修复，MSC 分泌的旁分泌介质是其大部分治疗益处的原因。最近，由活 MSC 及其分泌的细胞外基质组成的 MSC 片被报道可促进伤口愈合；然而，其细胞外基质是否单独可以加速伤口闭合尚不清楚。在这项研究中，分别从未条件化和 CoCl 条件化的 MSC 片中制备了 Nc-ECM 和 Cc-ECM，并在全层皮肤缺损小鼠模型中评估了它们的伤口愈合特性。我们的结果表明，Nc-ECM 通过早期脂肪细胞募集、快速上皮化、增强肉芽组织生长和增加血管生成，可显著促进伤口修复。此外，通过 HIF-1 的激活，CoCl 对 MSC 片的条件化极大地丰富了其 ECM 中的胶原 I、胶原 III、TGF-1、VEGF 和 bFGF，从而显著提高了其 ECM 在体内的伤口愈合能力。所有 Cc-ECM 处理的伤口在第 7 天完全愈合，而 Nc-ECM 处理的伤口愈合约 85.0%±8.6%，未处理的伤口仅愈合 69.8%±9.6%（<0.05）。因此，我们相信这种由化学缺氧 MSC 片制成的富含生长因子的细胞外基质具有临床转化的潜力，并将导致一种基于 MSC 的、经济有效的、可储存的用于伤口管理的生物材料。
