TGF-β1-containing exosomes derived from bone marrow mesenchymal stem cells promote proliferation, migration and fibrotic activity in rotator cuff tenocytes.

Abstract

ObjectiveThis study aimed to investigate effects of TGF-β1-containing exosomes derived from bone marrow mesenchymal stem cells (BMSC) on cell function of rotator cuff tenocytes and its implication to rotator cuff tear.MethodsThe primary BMSC and rotator cuff tenocytes were extracted and cultured. Identification of BMSC were performed by observing cell morphology and measurement of surface biomarkers by flow cytometry. BMSC-derived exosomes were extracted and identified by using electron microscopy, nanoparticle-tracking analysis (NTA) and western blotting. Cell proliferation and cell cycle were measured by CCK-8 assay and flow cytometry assay, respectively. Transwell assay was used for detection of tenocytes migration. The fibrotic activity of tenocytes was determined via qPCR and western blotting assays.ResultsBMSC and BMSC-derived exosomes were successfully extracted. Treatment of BMSC-derived exosomes or TGF-β1 promoted cell proliferation, migration and increased cell ratio of (S + G2/M) phases in tenocytes, as well as enhanced the expression levels of fibrotic activity associated proteins. However, inhibition of TGF-β1 by transfection of sh-TGF-β1 or treatment of TGFβR I/II inhibitor partially reversed the impact of BMSC-derived exosomes on tenocytes function.ConclusionTaken together, TGF-β1-containing exosomes derived from BMSC promoted proliferation, migration and fibrotic activity in rotator cuff tenocytes, providing a new direction for treatment of rotator cuff tendon healing.