Stem cell research & therapy · 2026
Exosomes derived from BMSCs regulate macrophage M1/M2 polarization and promoting tendon-bone healing through circRNA1052.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Guorong, Xu Juntao, Chen Zhuo, Wang Zichen, Lin Yizhou, Xu Xiaoliang, Lu Qian, Xu Qinguang, Sun Yifan, Chen Li, Xu Long, Li Xiongfeng, Wu Fengfeng
Аннотация
BACKGROUND: The 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.
METHODS: Primary 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.
RESULTS: We 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.
CONCLUSIONS: BMSCs-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.
METHODS: Primary 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.
RESULTS: We 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.
CONCLUSIONS: BMSCs-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.