Research progress on the application of stem cells and their derivatives in chronic wound repair
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摘要: 慢性创面因存在持续炎症、血管生成障碍、细胞功能失调及感染等因素,阻碍了自身正常愈合进程,不仅严重影响患者生活质量,也增加了社会经济负担。针对该类创面,传统疗法效果有限,且存在治疗周期长、费用高等问题。近年来,干细胞及其衍生物在创面修复领域的研究发展迅速。干细胞主要依赖其强大的旁分泌与免疫调节功能,辅以多向分化潜能,协同调控炎症反应、促进血管新生及胶原重塑,从而加速创面愈合。同时,基因修饰、三维培养及材料递送等工程化策略显著提升了干细胞的生物活性及环境适应性。此外,干细胞衍生物,尤其是外泌体,因具有低免疫原性、高稳定性、富含多种活性因子及易于工程化改造等优势,正成为新一代“无细胞治疗”策略,为复杂创面的精准再生提供了新思路。该文旨在综述慢性创面的病理机制、应用干细胞及其衍生物进行治疗的研究进展、相关工程化策略及临床应用挑战,以期为该领域提供参考。Abstract: Chronic wounds are characterised by factors including persistent inflammation, impaired angiogenesis, cellular dysfunction, and infection, which hinder the normal healing process, thereby not only severely compromising patients' quality of life but also imposing a substantial socioeconomic burden. For this type of wounds, conventional treatments are often limited in efficacy and associated with issues such as prolonged treatment duration and high costs. Recently, research on stem cells and their derivatives in the field of wound repair has been developing rapidly. Stem cells accelerate wound healing primarily through potent paracrine effects and immunomodulatory functions, complemented by multilineage differentiation potential, which synergistically modulate inflammation, promote angiogenesis, and facilitate collagen remodeling. Furthermore, engineering strategies including genetic modification, three-dimensional culture, and biomaterial-based delivery have significantly improved stem cell bioactivity and adaptability to the wound microenvironment. Concurrently, stem cell derivatives, particularly exosomes, have attracted increasing attention as a next-generation "cell-free" therapeutic strategy owing to their low immunogenicity, high stability, abundance of bioactive factors, and capacity for bioengineering modification. It offers a new approach to the precise regeneration of complex wounds. This review aims to review the pathological mechanisms underlying chronic wounds, research progress on therapeutic application of stem cells and their derivatives, engineering strategies, and translational challenges in clinical application, providing a reference for future research in the field.
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Key words:
- Stem cells /
- Exosomes /
- Tissue engineering /
- Stem cell derivatives /
- Chronic wounds /
- Engineering therapy /
- Delivery
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参考文献
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Table 1. 3种不同来源间充质干细胞的特性
间充质干细胞类型 优势 不足 主要分泌因子 骨髓来源的间充质干细胞 自我更新能力强,具有多向、长期分化潜能 需要侵入性获取,可及性有限,易被感染 VEGF、FGF、Ang-1、PGE2、IDO、IL-1RA、IL-8、IL-10、MCP-1 脂肪来源的间充质干细胞 可通过微创获取且产量高,具有低免疫原性、高细胞活力 自我更新能力有限,细胞干性受供体年龄影响,易发生复制性衰老,成骨与成软骨分化潜能较低 VEGF、HGF、TGF-β1、IL-10、FGF 脐带来源的间充质干细胞 为非侵入性获取,具有低免疫原性、低致瘤性,且不易被感染 获取途径受限,体内存活率低,成脂分化潜能尚存争议,成骨分化潜能较低 IL-1、IL-6、TNF-α、TSG-6、TIMP-1、TIMP-2、FGF、HGF 注：VEGF为血管内皮生长因子,FGF为成纤维细胞生长因子,Ang-1为血管生成素-1,PGE2为前列腺素-E2,IDO为吲哚胺2,3-双加氧酶,IL为白细胞介素,MCP-1为单核细胞趋化蛋白-1,HGF为肝细胞生长因子,TGF-β1为转化生长因子-β1,TNF-α为肿瘤坏死因子-α,TSG-6为TNF刺激基因-6,TIMP为组织金属蛋白酶抑制剂 
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Table 2. 部分间充质干细胞产品及其临床应用
间充质干细胞类型 批准国家或部门 产品名称 适应证 骨髓来源的间充质干细胞 美国 Ryoncil 儿科类固醇难治性急性移植物抗宿主病 韩国 Hearticellgram®-AMI 急性心肌梗死 日本 Stemirac 脊髓损伤 印度 Stempeucel 严重肢体缺血 伊朗 Mesestrocell 骨关节炎 脂肪来源的间充质干细胞 韩国 Queencell 皮下组织缺陷 欧洲药品管理局 Alofisel 克罗恩病 日本 Angel stem cell therapy 孤独症谱系障碍 脐带来源的间充质干细胞 韩国 Cartistem 膝骨关节炎 伊朗 AlloStemsin 肌萎缩侧索硬化症 中国 艾米迈托赛注射液 急性移植物抗宿主病 注：本表仅列举部分间充质干细胞产品及其公开信息,具体批准状态以相关监管机构最新信息为准
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