Evidence map›Paper›PMID 42057204›Full record

ArticleStem cell research & therapy2026

Exosomes derived from BMSCs regulate macrophage M1/M2 polarization and promoting tendon-bone healing through circRNA1052.

Guorong Wang, Juntao Xu, Zhuo Chen, Zichen Wang, Yizhou Lin, Xiaoliang Xu, Qian Lu, Qinguang Xu, Yifan Sun, Li Chen and 3 more

Abstract read
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In one paragraph

Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Guorong Wang *Department of Orthopaedics and Rehabilitation, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313000, Zhejiang, China.
Juntao Xu *Department of Orthopaedics, Huzhou Traditional Chinese Medicine Hospital, Huzhou, 313000, Zhejiang, China.
Zhuo Chen *Department of Orthopaedics and Rehabilitation, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313000, Zhejiang, China.
Zichen WangDepartment of Orthopaedics and Rehabilitation, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313000, Zhejiang, China.
Yizhou LinDepartment of Orthopaedics and Rehabilitation, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313000, Zhejiang, China.
Xiaoliang XuDepartment of Geriatrics, Huzhou Shushan Geriatric Hospital, Huzhou, 313000, Zhejiang, China.
Qian LuDepartment of Orthopaedics and Rehabilitation, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313000, Zhejiang, China.
Qinguang XuDepartment of Orthopaedics and Rehabilitation, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313000, Zhejiang, China.
Yifan SunDepartment of Orthopaedics and Rehabilitation, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313000, Zhejiang, China.
Li ChenDepartment of Orthopaedics and Rehabilitation, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313000, Zhejiang, China.
Long XuDepartment of Orthopaedics, Wuxing Hospital of Traditional Chinese and Western Medicine, Huzhou, 313000, Zhejiang, China.
Xiongfeng LiDepartment of Orthopaedics and Rehabilitation, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313000, Zhejiang, China. lyfwind@126.com.
Fengfeng WuDepartment of Orthopaedics and Rehabilitation, Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou Normal University, Huzhou, 313000, Zhejiang, China. wufengfeng@zju.edu.cn.

Funding

Huzhou Science and Technology Bureau 2024GY29Medical Health Science and Technology Project of Zhejiang Provincial Health Commission 2024KY426Traditional Chinese Medicine of Zhejiang Province 2023ZL681
6 · The paper itself

Abstract

backgroundThe high retear rate post tendon-bone reconstructive surgery is attributed to scar tissue replacing fibrocartilage, which compromises mechanical properties. Macrophages play a pivotal role in this process. Bone marrow mesenchymal stem cells-derived exosome (BMSCs-Exo) have emerged as a promising biological therapeutic approach. However, their role and underlying mechanisms in regulating macrophage polarization and tendon-bone healing require further investigation.

methodsPrimary macrophages were cultured, and a rat Achilles tendon-calcaneus reconstruction model was established, followed by BMSCs-Exo treatment. Exosome diameter was analyzed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Macrophage polarization was assessed via flow cytometry and immunofluorescence. ELISA measured cytokine levels, and immunohistochemistry evaluated molecular expression and distribution. Apoptosis levels were analyzed using TUNEL staining, and HE as well as Safranin O-Fast Green staining were utilized to examine tissue morphology and fibrocartilage regeneration at the tendon-bone junction. Biomechanical testing was used to assess joint stability. Western blot assessed molecular expression, while circRNA-seq was conducted to explore the impact of BMSCs-Exo on circRNA expression profiles in tendon-bone junction macrophages. qRT-PCR quantified circRNA and linear RNA levels, and fluorescence in situ hybridization (FISH) was used to observe circRNA expression and localization.

resultsWe isolated BMSCs-Exo and discovered its ability to promote macrophage polarization from M1 to M2 both in vitro and in vivo. This polarization was accompanied by a decrease in pro-inflammatory cytokines IL-1β and IL-12, and an increase in anti-inflammatory cytokines TGF-β1 and IL-10. Additionally, BMSCs-Exo significantly enhanced tendon-bone healing, improved the tissue morphology at the tendon-bone junction, increased chondrocyte and fibrocartilage formation, upregulated the expression of collagen I, Aggrecan, and collagen II, improved joint stability. However, macrophage depletion using Clodronate liposomes (CL) effectively inhibited the therapeutic effects of BMSCs-Exo. Mechanistic studies revealed that BMSCs-Exo transfers circRNA1052 to macrophages, driving their polarization from M1 to M2, thereby mitigating early inflammatory responses and enhancing tissue repair during later stages, ultimately facilitating tendon-bone healing. Furthermore, downregulation of circRNA1052 expression attenuated the beneficial effects of BMSCs-Exo.

conclusionsBMSCs-Exo transfer circRNA1052 to macrophages, suppressing their pro-inflammatory phenotype and promoting polarization toward the tissue-repairing M2 phenotype. This process enhances fibrocartilage formation, improves tissue morphology, and accelerates tendon-bone healing.

Indexed as

Achilles TendonExosomesMacrophagesMesenchymal Stem CellsRNA, CircularWound HealingAnimalsMaleRatsRats, Sprague-DawleyRNA, CircularBMSCscircRNA1052ExosomeMacrophageTendon-bone healing

Identifiers

PMID42057204
PMCPMC13270673

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