Liu Chenyang, Lu Yichi, Du Pan, Yang Fengbo, Guo Peng, Tang Xiaoyu, Diao Ling, Lu Guozhong
Nanjng University of Traditional Chinese Medicine, Nanjng, Jiangsu, China.
Engineering Research Center of the Ministry of Education for Wound Repair Technology, Jiangnan University, The Affiliated Hospital of Jiangnan University, Jiangsu, China.
Regen Ther. 2022 Jul 31;21:192-200. doi: 10.1016/j.reth.2022.06.009. eCollection 2022 Dec.
Numerous studies have shown that mesenchymal stem cells (MSCs) promote cutaneous wound healing via paracrine signaling. Our previous study found that the secretome of MSCs was significantly amplified by treatment with IFN-γ and TNF-α (IT). It has been known that macrophages are involved in the initiation and termination of inflammation, secretion of growth factors, phagocytosis, cell proliferation and collagen deposition in wound, which is the key factor during wound healing. In the present study, we used a unique supernatant of MSCs from human umbilical cord-derived MSCs (UC-MSCs) pretreated with IT, designated S-IT MSCs, to explore whether S-IT MSCs have a better effect on improving wound healing by improving the biological function of macrophages than the control supernatant of MSCs (S-MSCs).
In the present study, we used a unique supernatant of MSCs pretreated with IT subcutaneously injected into a mice total skin excision. We evaluated the effect of S-IT MSCs on wound healing and the quality of wound repair via promoting macrophages migration and M2 polarization in vivo. In addition, the effect of S-IT MSCs on macrophages migration, converting toward M2 phenotype and phagocytosis were also investigated in vitro.
Indeed, S-IT MSCs were found to be more potent in promoting macrophage migration, M2 polarization, phagocytosis, and promoting wound closure than S-MSCs during the wound repair. High levels of CCL2 and IL-6 were found in S-IT MSCs, which indicated that the optimization of macrophage function by S-IT MSCs may be achieved through their high expression of CCL2 and IL-6.
Our results suggest that the beneficial paracrine effect of MSCs on wound healing can be amplified by pretreatment with IT, which may represent a new strategy for optimizing the therapeutic effect of MSCs on wound healing.
大量研究表明，间充质干细胞（MSCs）通过旁分泌信号促进皮肤伤口愈合。我们之前的研究发现，用干扰素-γ和肿瘤坏死因子-α（IT）处理可显著增强MSCs的分泌组。众所周知，巨噬细胞参与炎症的起始和终止、生长因子的分泌、吞噬作用、细胞增殖以及伤口中的胶原沉积，这是伤口愈合过程中的关键因素。在本研究中，我们使用了经IT预处理的人脐带间充质干细胞（UC-MSCs）的独特上清液，即S-IT MSCs，以探讨S-IT MSCs是否比MSCs的对照上清液（S-MSCs）通过改善巨噬细胞的生物学功能对促进伤口愈合具有更好的效果。
在本研究中，我们将经IT预处理的MSCs的独特上清液皮下注射到全层皮肤切除的小鼠体内。我们通过促进体内巨噬细胞迁移和M2极化来评估S-IT MSCs对伤口愈合和伤口修复质量的影响。此外，还在体外研究了S-IT MSCs对巨噬细胞迁移、向M2表型转化和吞噬作用的影响。
确实，在伤口修复过程中，发现S-IT MSCs在促进巨噬细胞迁移、M2极化、吞噬作用以及促进伤口闭合方面比S-MSCs更有效。在S-IT MSCs中发现高水平的CCL2和IL-6，这表明S-IT MSCs对巨噬细胞功能的优化可能是通过其CCL2和IL-6的高表达实现的。
我们的结果表明，MSCs对伤口愈合的有益旁分泌作用可通过IT预处理来增强，这可能代表了一种优化MSCs对伤口愈合治疗效果的新策略。
