Exosomes derived from BMSCs regulate macrophage M1/M2 polarization and promoting tendon-bone healing through
Guorong Wang1, Juntao Xu2, Zhuo Chen1
1Department 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.
Stem Cell Research & Therapy
|April 30, 2026
Summary
Bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exo) promote tendon-bone healing by shifting macrophages to an M2 phenotype via circRNA1052 transfer. This enhances tissue repair and reduces inflammation, improving surgical outcomes.
Area of Science:
- Regenerative Medicine
- Biomaterials Science
- Immunology
Background:
- High retear rates after tendon-bone surgery stem from scar tissue formation, compromising mechanical integrity.
- Macrophages are key players in the inflammatory response and tissue repair post-surgery.
- Bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exo) show therapeutic potential but require mechanistic understanding for tendon-bone healing.
Purpose of the Study:
- To investigate the role of BMSCs-Exo in regulating macrophage polarization for improved tendon-bone healing.
- To elucidate the underlying molecular mechanisms, particularly the involvement of circular RNAs (circRNAs), in BMSCs-Exo mediated tendon-bone repair.
Main Methods:
- Established a rat Achilles tendon-calcaneus reconstruction model and treated with BMSCs-Exo.
- Analyzed exosome characteristics using TEM and NTA.
- Assessed macrophage polarization (M1/M2) via flow cytometry and immunofluorescence.
- Evaluated cytokine levels (ELISA), tissue morphology (HE, Safranin O-Fast Green), and biomechanical stability.
- Investigated circRNA expression profiles in macrophages using circRNA-seq and qRT-PCR, with FISH for localization.
Main Results:
- BMSCs-Exo treatment promoted M1 to M2 macrophage polarization, decreasing pro-inflammatory cytokines (IL-1β, IL-12) and increasing anti-inflammatory cytokines (TGF-β1, IL-10).
- This polarization enhanced tendon-bone healing, improved tissue morphology, increased fibrocartilage formation, and boosted joint stability.
- Macrophage depletion abrogated BMSCs-Exo therapeutic effects, confirming their critical role.
- Mechanistically, BMSCs-Exo transferred circRNA1052 to macrophages, driving M2 polarization and facilitating healing; circRNA1052 downregulation diminished these benefits.
Conclusions:
- BMSCs-Exo facilitate tendon-bone healing by transferring circRNA1052 to macrophages, suppressing M1 pro-inflammatory responses and promoting M2 tissue-repair phenotypes.
- This circRNA-mediated macrophage reprogramming enhances fibrocartilage formation and accelerates tendon-bone healing, offering a promising therapeutic strategy.
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