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已发表论文
反复给予间充质干细胞通过旁分泌介导的巨噬细胞重编程减轻超高分子量聚乙烯磨损颗粒诱导的骨溶解
Authors Ding K, Fan D, Dong A, Ma C, Zeng T, Huang Z, Yang Y, Song K
Received 6 August 2025
Accepted for publication 27 October 2025
Published 11 November 2025 Volume 2025:18 Pages 15717—15735
DOI https://doi.org/10.2147/JIR.S557244
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Ujjwol Risal
Kun Ding,1,* Dechao Fan,2,* Ao Dong,1 Chicheng Ma,1 Teng Zeng,3 Zhen Huang,4 Yinghao Yang,5 Keguan Song1
1The Third Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Orthopedics, The First People’s Hospital of Jingzhou, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, People’s Republic of China; 4Department of Joint Surgery, Affiliated Minzu University Hospital of Hubei Minzu University, Enshi, Hubei, People’s Republic of China; 5Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Keguan Song, The Third Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, Heilongjiang, 150001, People’s Republic of China, Email songkeguan1965@sina.com
Purpose: Periprosthetic osteolysis (PPO) induced by ultra-high molecular weight polyethylene (UHMWPE) particles remains a major clinically challenging problem in joint arthroplasty. This study investigated whether local delivery of bone marrow mesenchymal stem cells (BMSCs) could alleviate UHMWPE-induced bone destruction by modulating macrophage polarization.
Methods: In vivo, a murine calvarial osteolysis model was established and divided into four groups: Sham, UHMWPE-induced osteolysis (PIO), single BMSC injection (BMSCs-1), and repeated BMSC injection (BMSCs-2) groups. In vitro, RAW264.7 macrophages were treated under five conditions: RAW264.7 alone, BMSCs alone, RAW264.7+BMSCs, RAW264.7 + UHMWPE, and RAW264.7 + UHMWPE + BMSCs in a transwell co-culture system. Bone parameters (BMD, BV/TV, Tb.Th, and Tb.N) were evaluated by micro-CT; Macrophage polarization and cytokine expression were assessed by histology, immunohistochemistry (IHC), flow cytometry, ELISA, and immunofluorescence.
Results: In vivo, BMSC administration markedly improved bone parameters and mitigated UHMWPE-induced osteolysis, with repeated dosing showing more efficacy than a single dose compared to the PIO group. BMSC treatment suppressed M1 (CD80⁺) macrophage infiltration, enhanced M2 (CD206⁺) polarization, and rebalanced cytokine expression by reducing TNF-α and increasing IL-10 levels. In vitro, the BMSC transwell co-culture system consistently promoted M2 polarization and anti-inflammatory cytokine secretion in UHMWPE-stimulated macrophages, confirming the paracrine-mediated immunomodulatory effect.
Conclusion: Local BMSC therapy, particularly with repeated dosing, effectively attenuated UHMWPE-induced osteolysis by reprogramming macrophage polarization through paracrine signaling. These findings highlight a potential translational strategy for stem cell-based treatment of periprosthetic osteolysis.
Keywords: osteolysis, macrophage activation, bone marrow mesenchymal stem cells, polyethylene, inflammation
1The Third Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Orthopedics, The First People’s Hospital of Jingzhou, First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, People’s Republic of China; 4Department of Joint Surgery, Affiliated Minzu University Hospital of Hubei Minzu University, Enshi, Hubei, People’s Republic of China; 5Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Keguan Song, The Third Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, Heilongjiang, 150001, People’s Republic of China, Email songkeguan1965@sina.com
Purpose: Periprosthetic osteolysis (PPO) induced by ultra-high molecular weight polyethylene (UHMWPE) particles remains a major clinically challenging problem in joint arthroplasty. This study investigated whether local delivery of bone marrow mesenchymal stem cells (BMSCs) could alleviate UHMWPE-induced bone destruction by modulating macrophage polarization.
Methods: In vivo, a murine calvarial osteolysis model was established and divided into four groups: Sham, UHMWPE-induced osteolysis (PIO), single BMSC injection (BMSCs-1), and repeated BMSC injection (BMSCs-2) groups. In vitro, RAW264.7 macrophages were treated under five conditions: RAW264.7 alone, BMSCs alone, RAW264.7+BMSCs, RAW264.7 + UHMWPE, and RAW264.7 + UHMWPE + BMSCs in a transwell co-culture system. Bone parameters (BMD, BV/TV, Tb.Th, and Tb.N) were evaluated by micro-CT; Macrophage polarization and cytokine expression were assessed by histology, immunohistochemistry (IHC), flow cytometry, ELISA, and immunofluorescence.
Results: In vivo, BMSC administration markedly improved bone parameters and mitigated UHMWPE-induced osteolysis, with repeated dosing showing more efficacy than a single dose compared to the PIO group. BMSC treatment suppressed M1 (CD80⁺) macrophage infiltration, enhanced M2 (CD206⁺) polarization, and rebalanced cytokine expression by reducing TNF-α and increasing IL-10 levels. In vitro, the BMSC transwell co-culture system consistently promoted M2 polarization and anti-inflammatory cytokine secretion in UHMWPE-stimulated macrophages, confirming the paracrine-mediated immunomodulatory effect.
Conclusion: Local BMSC therapy, particularly with repeated dosing, effectively attenuated UHMWPE-induced osteolysis by reprogramming macrophage polarization through paracrine signaling. These findings highlight a potential translational strategy for stem cell-based treatment of periprosthetic osteolysis.
Keywords: osteolysis, macrophage activation, bone marrow mesenchymal stem cells, polyethylene, inflammation