Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair.
Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair.
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作者：
Chen L;Xing Q;Zhai Q;Tahtinen M;Zhou F;Chen L;Xu Y;Qi S;Zhao F
中厚皮片移植(STSG)是全厚自体皮片(FTG)或皮瓣移植不适用时全厚创面修复的标准方法之一。STSG与真皮替代物联合移植可提高疗效，但因早期血供不足，导致移植物坏死、纤维化，效果不佳。人骨髓间充质干细胞(HMSC)片能够加速伤口愈合过程。我们推测，通过提供更多功能的血管生成因子和预形成的微血管，预血管化的hMSC片材将进一步促进再生。本研究将体外培养的人骨髓间充质干细胞(HMSC)片(HCS)和预制血管的hMSC细胞片(PHCS)植入大鼠全层皮肤创伤模型。结果表明，与STSG对照组相比，HCS和PHCS植入物显著减少了皮肤收缩，改善了美容效果。PHCS组出血、坏死最少，炎性细胞浸润最少。它还在早期阶段诱导了最高的新生血管，从而建立了强大的血液微循环，以支持移植物存活和组织再生。此外，PHCS移植物保留了最多的皮肤附属物，包括毛囊和皮脂腺，并形成了最小的表皮厚度。PHCS组的治疗效果优于对照组，这是由于在创面修复过程中，血管形成前的细胞膜中的生长因子和细胞因子的存在增加，从而发挥了有益的旁分泌信号。因此，STSG和PHCS植入相结合的策略在全层皮肤创面的再生治疗中是一种很有前途的方法。
Split thickness skin graft (STSG) implantation is one of the standard therapies for full thickness wound repair when full thickness autologous skin grafts (FTG) or skin flap transplants are inapplicable. Combined transplantation of STSG with dermal substitute could enhance its therapeutic effects but the results remain unsatisfactory due to insufficient blood supply at early stages, which causes graft necrosis and fibrosis. Human mesenchymal stem cell (hMSC) sheets are capable of accelerating the wound healing process. We hypothesized that pre-vascularized hMSC sheets would further improve regeneration by providing more versatile angiogenic factors and pre-formed microvessels. In this work, in vitro cultured hMSC cell sheets (HCS) and pre-vascularized hMSC cell sheets (PHCS) were implanted in a rat full thickness skin wound model covered with an autologous STSG. Results demonstrated that the HCS and the PHCS implantations significantly reduced skin contraction and improved cosmetic appearance relative to the STSG control group. The PHCS group experienced the least hemorrhage and necrosis, and lowest inflammatory cell infiltration. It also induced the highest neovascularization in early stages, which established a robust blood micro-circulation to support grafts survival and tissue regeneration. Moreover, the PHCS grafts preserved the largest amount of skin appendages, including hair follicles and sebaceous glands, and developed the smallest epidermal thickness. The superior therapeutic effects seen in PHCS groups were attributed to the elevated presence of growth factors and cytokines in the pre-vascularized cell sheet, which exerted a beneficial paracrine signaling during wound repair. Hence, the strategy of combining STSG with PHCS implantation appears to be a promising approach in regenerative treatment of full thickness skin wounds.
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影响因子：
11.4
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