Huang Yi-Zhou, Gou Min, Da Lin-Cui, Zhang Wen-Qian, Xie Hui-Qi
Laboratory of Stem Cell and Tissue Engineering, Orthopaedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China.
Tissue Eng Part B Rev. 2020 Dec;26(6):555-570. doi: 10.1089/ten.TEB.2019.0351. Epub 2020 May 20.
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. Impact statement Chronic wounds persist as a significant health care problem, particularly with increasing number of patients and the lack of efficient treatments. The main goal of this article is to provide an overview of current status of mesenchymal stem cell (MSC)-based therapy for chronic wounds. The roles of MSCs in skin wound healing, as revealed in a large number of animal studies, are detailed. A critical view is made on the clinical application of MSCs for lower extremity ulcers, pressure sores, and radiation burns. Main challenges that confront future clinical applications are discussed, which hopefully contribute to innovations in MSC-based wound treatment.
实现具有解剖学和功能完整性的皮肤伤口愈合，尤其是在慢性病理条件下，仍然是一项巨大的挑战。由于间充质干细胞（MSCs）具有出色的再生潜力，许多研究对其进行了探索，以确定其对难治性疾病的愈合能力。在本文中，我们回顾了当前基于MSCs治疗慢性伤口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，大量动物研究揭示了MSCs在慢性伤口愈合中的多种作用和益处。MSCs治疗可增强血管生成、促进上皮再形成、改善肉芽组织并加速伤口闭合。有一些证据表明MSCs可转分化为皮肤细胞。然而，MSCs的愈合作用主要取决于其旁分泌作用，这种作用可缓解慢性伤口的恶劣微环境并调节局部细胞反应。与临床前研究结果一致，一些临床试验表明，在慢性伤口（主要是下肢溃疡、压疮和放射性烧伤）中移植MSCs后伤口愈合得到改善。然而，这些临床试验存在一些局限性，尤其是患者数量少和方法不完善。因此，为了更好地确定基于MSCs的伤口治疗的安全性和有效性，未来需要进行大规模对照多中心试验。此外，为了建立强有力的临床证据库，建议采用标准化方案，尤其是MSCs的培养和质量控制。总之，基于目前的数据，基于MSCs的治疗是慢性伤口一种有前景的治疗选择。影响声明慢性伤口仍然是一个重大的医疗保健问题，特别是随着患者数量的增加和缺乏有效的治疗方法。本文的主要目的是概述基于间充质干细胞（MSCs）治疗慢性伤口的现状。详细介绍了大量动物研究中揭示的MSCs在皮肤伤口愈合中的作用。对MSCs在下肢溃疡、压疮和放射性烧伤中的临床应用进行了批判性审视。讨论了未来临床应用面临的主要挑战，希望这有助于基于MSCs的伤口治疗创新。
