中国现代医学杂志2026，Vol.36Issue(3)：58-65,8.DOI:10.3969/j.issn.1005-8982.2026.03.009
基于靶向肽改造的间充质干细胞用于膝骨关节炎治疗的作用机制与研究进展
Mechanism and research progress of mesenchymal stem cells modified with targeted peptides for the treatment of knee osteoarthritis
摘要
Abstract
Knee osteoarthritis(KOA),a highly disabling degenerative joint disease,cannot have its cartilage damage reversed by traditional treatments.Although mesenchymal stem cells(MSCs)possess the potential for chondrogenic differentiation and immunomodulation,native MSCs are plagued by several bottlenecks,including low homing efficiency(with less than 5%reaching the injured area),short retention time in the joint cavity(less than 24 hours),and abnormal hypertrophic differentiation(with high expression of Col10a1/Runx2)in the inflammatory microenvironment.This review proposed a core strategy of engineering MSCs with targeting peptides:Targeted modification:Through bionic design,the surface of MSCs was modified using click chemistry or membrane hydrophobic insertion methods,which significantly improved the homing efficiency(with the local concentration increased by 3-fold)and retention time(≥7 days).Synergistic delivery system:MSCs were integrated with nanocarriers to form"dual-engineered MSCs",which simultaneously and precisely regulated chondrogenic differentiation and remodeled the immune microenvironment.Preclinical studies(on osteoarthritis mice/human cartilage explants)showed that engineered MSCs promoted the regeneration of cartilage matrix and improved pathological scores.Clinical trials confirmed that allogeneic MSCs and combined therapy could relieve pain,improve function,and delay disease progression.This therapy was recommended in China's Clinical Practice Guidelines for Osteoarthritis(2024 Edition)for the stepped treatment of early-stage KOA.For clinical translation,issues such as the stability of targeting peptides,the long-term safety of nanocarriers,and standardization need to be addressed.Future directions include the development of enzyme-resistant peptides(via D-amino acid substitution),cell-free therapy based on targeting peptides and exosomes,artificial intelligence-assisted peptide design,as well as the establishment of automated production processes and multi-dimensional efficacy standards.These efforts aim to promote engineered MSCs to become a disease-modifying osteoarthritis drug for moderate-to-early-stage KOA.关键词
膝骨关节炎/间充质干细胞/靶向肽/归巢/软骨再生/免疫调节/工程化/疾病修饰疗法Key words
knee osteoarthritis/mesenchymal stem cells/targeting peptide/homing/cartilage regeneration/immunomodulation/engineering/disease-modifying therapy分类
医药卫生引用本文复制引用
杨志超,左立新..基于靶向肽改造的间充质干细胞用于膝骨关节炎治疗的作用机制与研究进展[J].中国现代医学杂志,2026,36(3):58-65,8.基金项目
河南省医学科技攻关计划项目(No:LHGJ20240491) （No:LHGJ20240491）
