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中华关节外科杂志(电子版) ›› 2025, Vol. 19 ›› Issue (05) : 597 -608. doi: 10.3877/cma.j.issn.1674-134X.2025.05.010

综述

软骨组织工程应用脱细胞干细胞基质的研究进展
魏志鑫1, 宋本静2, 蒋丽2, 余清卿2, 谢庆云2, 廖冬发2, 陈松2,3,†()   
  1. 1610031　成都，西南交通大学医学院
    2610083　成都，西南交通大学医学院·西部战区总医院骨科
    3610083　成都，四川省组织应激损伤与功能修复重点实验室
  • 收稿日期:2025-01-27 出版日期:2025-10-01
  • 通信作者: 陈松
  • 基金资助:
    四川省自然科学基金面上项目(2024NSFSC0673); 成都市医学科研课题(202433); 四川省中医药管理局科学技术研究专项项目(25MSZX489)

Research progress of decellularized stem cell matrix and its applications in cartilage tissue engineering

Zhixin Wei1, Benjing Song2, Li Jiang2, Qingqing Yu2, Qingyun Xie2, Dongfa Liao2, Song Chen2,3,†()   

  1. 1College of Medicine, Southwest Jiaotong University, Chengdu 610031, China
    2Department of Orthopaedics, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610031, China
    3Tissue Stress Injury and Functional Repair Key Laboratory of Sichuan Province, Chengdu 610083, China
  • Received:2025-01-27 Published:2025-10-01
  • Corresponding author: Song Chen
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引用本文：

魏志鑫, 宋本静, 蒋丽, 余清卿, 谢庆云, 廖冬发, 陈松. 软骨组织工程应用脱细胞干细胞基质的研究进展[J/OL]. 中华关节外科杂志(电子版), 2025, 19(05): 597-608.

Zhixin Wei, Benjing Song, Li Jiang, Qingqing Yu, Qingyun Xie, Dongfa Liao, Song Chen. Research progress of decellularized stem cell matrix and its applications in cartilage tissue engineering[J/OL]. Chinese Journal of Joint Surgery(Electronic Edition), 2025, 19(05): 597-608.

关节软骨因缺乏血管和神经，其损伤后的自我修复能力极其有限，干细胞组织工程技术为其再生提供了新的治疗前景。间充质干细胞（MSCs）来源有限，在体外扩增过程中易发生复制性衰老，伴随成软骨分化潜能下降。脱细胞干细胞基质（DSCM）是一种新兴的天然活性生物材料，已被证实可促进MSCs增殖，增强其成软骨分化能力，同时抑制复制性衰老与炎症反应，在软骨组织工程中有广泛应用前景。DSCM在软骨修复中的效果受细胞来源、制备方法及使用形式等因素的影响，且其在小动物模型中已成功实现促进软骨再生，展现出良好的临床转化潜力。本文综述了体外扩增的MSCs所沉积的DSCM在调控MSCs增殖、成软骨分化潜能、复制性衰老及炎症反应方面的研究进展及其潜在的分子机制，旨在为干细胞组织工程技术在软骨损伤修复中的应用提供新的思路和策略。

关键词: 脱细胞细胞外基质, 间质干细胞, 软骨, 软骨发生, 组织工程, 再生医学, 信号传导

Articular cartilage has limited self-healing capacity due to the absence of blood vessels and nerves. Stem cell-based tissue engineering offers promising therapies for cartilage repair, but mesenchymal stem cell (MSC) sources are limited, and replicative senescence and decreased chondrogenic differentiation potential occur during in vitro expansion. Decellularized stem cell matrix (DSCM), a bioactive material, enhances MSC proliferation, chondrogenic differentiation, and resistance to replicative senescence and inflammation, making it a promising tool in cartilage tissue engineering. The regenerative efficacy of DSCM in cartilage repair is modulated by variables such as the cell source, fabrication techniques, and modes of application. Notably, its successful application in promoting cartilage regeneration in small animal models underscores its substantial potential for clinical translation. This review highlighted the impact of DSCM deposited by expanded MSCs in vitro on MSC proliferation, chondrogenic differentiation, replicative senescence, and inflammatory response, providing insights into its potential for cartilage repair through stem cell-based tissue engineering.

Key words: Decellularized extracellular matrix, Mesenchymal stem cell, Cartilage, Chondrogenesis, Tissue engineering, Regenerative medicine, Signal transduction
表1 DSCM中主要成分及其在软骨再生中的生物学功能
Table 1 Major components of DSCM and their biological functions in cartilage regeneration
DSCM成分 相关功能
COL Ⅰ[4] 促进细胞增殖以及增强抗衰老能力
COL Ⅱ[14] 促进相关细胞成软骨分化
COL Ⅲ[15] 促进相关细胞成软骨分化
纤维连接蛋白[12] 为细胞及其他活性分子提供粘附位点
层粘连蛋白[16] 参与基底膜结构形成及促进相关细胞成软骨分化
弹性蛋白[17] 抵抗反复拉伸力，维持组织弹性
GAG[18] 与蛋白质结合成蛋白聚糖，有助于调控细胞行为及生长发育
HSPG2[19] 促进相关细胞成软骨分化
图1 DSCM与细胞相互作用对其固有特性及成软骨分化潜能的影响注：DSCMs-脱细胞干细胞基质；IL-白细胞介素；TNF-肿瘤坏死因子；iNOS-诱导型一氧化氮合酶
Figure 1 Effect of DSCM interaction with cells on their intrinsic properties and chondrogenic potential.
表2 DSCM预处理策略对靶向细胞软骨生成分化潜能的影响
Table 2 Impact of DSCM preconditioning strategies on the chondrogenic potential of target cells
DSCM来源 靶细胞 结果
成人SDSCs、ADSCs、UDSCs[25,36,47,48] 成人SDSCs SDSCs经过DSCMs预处理后，在成软骨过程中SOX9、COL2A1等相关软骨基因表达更高，同时COL1A1、COL10A1等相关肥大基因表达也进一步上调。
猪SDSCs[3,49] 猪NPCs、SDSCs 细胞经DSCM预处理后，成软骨相关基因COL2A1表达更高，同时肥大基因ALPL表达亦上调。
成人和胎儿SDSCs[32,40,50] 胎儿SDSCs 胎儿细胞经成人或胎儿DSCM预处理后，成软骨过程中COL2A1、ACAN等基因表达均提升，且经成人DSCM预处理后，这些基因的表达进一步增强。
成人IFPSCs（转染或未转染hTERT、SV40LT过表达）[29,31] 成人IFPSCs IFPSCs经DSCM预处理后，成软骨诱导时SOX9、COL2A1等成软骨基因表达显著上调，同时肥大基因COL10A1表达亦显著提高。
兔IFPSCs、成人SDSCs、ADSCs、UDSCs[22,26] 兔IFPSCs 兔IFPSCs经DSCM预处理后，在成软骨诱导过程中，SOX9和ACAN等成软骨基因表达显著上调。
成人BMSCs、UDSCs[28,39] 成人BMSCs BMSCs经DSCM预处理后，其成软骨潜能增强，特别是在UDSCs产生的DSCM预处理下，成软骨诱导过程中成软骨相关基因表达最高。
猪SDSCs[42] 猪NPCs 猪NPCs在DSCM上扩增后，软骨诱导过程中SOX9、COL2A1、ACAN等成软骨基因表达升高，同时肥大化基因COL10A1也上调。
猪、人、兔BMSCs[44,45,46] 猪、人、兔软骨细胞 软骨细胞经DSCMs预处理后，成软骨基因合成增强，同时抑制纤维化相关基因COL1A1的表达。
成人ADSCs（转染或未转染SV40LT过表达）[30] 成人ADSCs ADSCs经过DSCM预处理后，在成软骨诱导过程中，SOX9、COL2A1、ACAN等成软骨基因表达未显著上调，与Plastic对照组相比无明显差异
成人BMSCs、UDSCs[28] 成人UDSCs UDSCs在成软骨过程中，无论是否经过DSCMs预处理，其形成的软骨球在成软骨诱导时逐渐缩小，最终消失。
图2 DSCM影响细胞成软骨过程的关键分子机制，重点涉及WNT和MAPK信号通路注：DSCM-脱细胞干细胞基质；ERK-细胞外调节蛋白激酶；JnK- c-Jun氨基末端激酶；Cyclin-细胞周期蛋白；SIRT-沉默信息调控因子
Figure 2 Key molecular mechanisms of DSCM affecting chondrogenesis, with emphasis on WNT and MAPK signaling pathways
图3 DSCM的制备、DSCM预处理策略，以及DSCM衍生支架在软骨修复和再生中的应用注：DSCMs-脱细胞干细胞基质；ECM-细胞外基质
Figure 3 DSCM preparation, DSCM preconditioning strategies, and the application of DSCM derived scaffolds in cartilage repair and regeneration
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