This article is excerpted from the ACS Cent. Sci. 2024, 10, 1976−1979 by Wound World.
Wenwen Wang1,‡, , Pu Liu2,3,‡, , Wendi Zhu1,‡, , Tianwei Li2, , Ying Wang1, , Yujie Wang1, , Jun Li1, , Jie Ma2,*, ,Ling Leng1,*,
1 Stem Cell and Regenerative Medicine Lab, Institute of Clinical Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
2 State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China
3 Chongqing Key Laboratory on Big Data for Bio Intelligence, Chongqing University of Posts and Telecommunications, Chongqing 400065, China ‡ These authors contributed equally.
* Correspondence: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (J. Ma); 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 (L. Leng)
Abstract
Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized infammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells, and fbroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC)-derived skin organoids combined with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment signifcantly accelerated wound healing by reducing early infammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fbroblasts, signifcantly reduced fbroblast-to-myofbroblast transition by regulating the integrin α5β1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfgurement and skin dysfunction caused by frostbite.
Keywords skin frostbite, frostbite treatment, human-induced pluripotent stem cell, skin organoids, single-cell transcriptomics
东莞康华医院国际造口治疗师，采用全球倡导的伤口湿性愈合疗法和造口专科护理新技术，在糖尿病溃疡足、下肢动/静脉溃疡、骨髓炎、外科术后感染/脂肪液化、肿瘤伤口、放射性皮炎、痛风破溃感染、压力性损伤（压疮）、液体外渗、造口并发症、失禁、瘘管等方面提供专业化的诊治、咨询及健康教育。
从事骨科临床工作和外科学教学工作30年。擅长骨关节疾病、四肢骨折和手外伤的保守治疗、手术治疗（关节置换手术、四肢骨折内固定手术、创伤修复手术）；各类创面的修复：包括糖尿病足、难治性痛风破溃感染伤口、创伤术后伤口不愈合。
长期从事影像诊断和介入放射学诊疗工作，擅长肿瘤和血管病的介入治疗。
佛山市禅城区中心医院慢性伤口造口专科主任。
伤口世界平台生态圈，以“关爱人间所有伤口患者”为愿景，连接、整合和拓展线上和线下的管理慢性伤口的资源，倡导远程、就近和居家管理慢性伤口，解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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