Healing skin wounds with anatomic and functional integrity, especially under chronic pathological conditions, remain an enormous challenge. Due to their outstanding regenerative potential, mesenchymal stem cells (MSCs) have been explored in many studies to determine the healing ability for difficult-to-treat diseases. In this article, we review current animal studies and clinical trials of MSC-based therapy for chronic wounds, and discuss major challenges that confront future clinical applications. We found that a wealth of animal studies have revealed the versatile roles and the benefits of MSCs for chronic wound healing. MSC treatment results in enhanced angiogenesis, facilitated reepithelialization, improved granulation, and accelerated wound closure. There are some evidences of the transdifferentiation of MSCs into skin cells. However, the healing effect of MSCs depends primarily on their paracrine actions, which alleviate the harsh microenvironment of chronic wounds and regulate local cellular responses. Consistent with the findings of preclinical studies, some clinical trials have shown improved wound healing after transplantation of MSCs in chronic wounds, mainly lower extremity ulcers, pressure sores, and radiation burns. However, there are some limitations in these clinical trials, especially a small number of patients and imperfect methodology. Therefore, to better define the safety and efficiency of MSC-based wound therapy, large-scale controlled multicenter trials are needed in the future. In addition, to build a robust pool of clinical evidence, standardized protocols, especially the cultivation and quality control of MSCs, are recommended. Altogether, based on current data, MSC-based therapy represents a promising treatment option for chronic wounds.

中文翻译：

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用于慢性伤口愈合的间充质干细胞：临床前和临床研究的现状。

愈合具有解剖和功能完整性的皮肤伤口，尤其是在慢性病理条件下，仍然是一个巨大的挑战。由于其出色的再生潜力，许多研究已经探索了间充质干细胞 (MSC) 以确定难以治疗的疾病的治愈能力。在本文中，我们回顾了当前基于 MSC 的慢性伤口疗法的动物研究和临床试验，并讨论了未来临床应用面临的主要挑战。我们发现，大量的动物研究揭示了 MSCs 在慢性伤口愈合中的多功能作用和益处。MSC 治疗可增强血管生成、促进再上皮化、改善肉芽形成和加速伤口闭合。有一些证据表明 MSCs 转分化为皮肤细胞。然而，间充质干细胞的愈合效果主要取决于它们的旁分泌作用，它可以缓解慢性伤口的恶劣微环境并调节局部细胞反应。与临床前研究的结果一致，一些临床试验表明在慢性伤口中移植 MSCs 后伤口愈合得到改善，主要是下肢溃疡、压疮和辐射烧伤。然而，这些临床试验存在一定的局限性，尤其是患者人数少、方法学不完善。因此，为了更好地定义基于 MSC 的伤口治疗的安全性和效率，未来需要进行大规模的多中心对照试验。此外，为了建立强大的临床证据库，建议采用标准化协议，尤其是 MSCs 的培养和质量控制。共，