Endometrial Mesenchymal Stem Cell-Derived Exosome Promote Endothelial Cell Angiogenesis in a Dose Dependent Manner: A New Perspective on Regenerative Medicine and Cell-Free Therapy

Background: Endometrium is recently introduced as an available source of mesenchymal stem cells (EnMSCs), which can be obtained without anesthesia and side effects. Regarding the issues and complexities of cell-based therapies, exosomes gain tremendous attention as a novel tool for cell-free therapies. Although several clinical trials are recently established based on therapeutic potential of EnMSCs, biological roles of EnMSC-derived exosomes are still unclear. Methods: The current study was conducted to investigate the potential effects of EnMSC- derived exosomes on proliferation, migration, and angiogenesis of human umbilical cord vein endothelial cells (HUVECs). For this purpose, EnMSCs and then EnMSC-derived exosomes were isolated and characterized. MTT assay and wound healing assay as well as tube formation assay were applied. Results: The collected data showed that EnMSC-derived exosomes significantly increased proliferation, migration, and angiogenesis of HUVECs. It was observed that the effects of exosomes were applied in a dose dependent manner. In addition, expression analysis by quantitative real-time PCR showed that increased expression of proliferation and angiogenesis genes in HUVECs were treated with EnMSC-derived exosomes in a dose dependent manner. Conclusions: The current study results showed that EnMSC-derived exosomes can exert biological effects such as their source cells and become new candidates for cell-free therapies. Taken together, increased angiogenesis makes EnMSC-derived exosomes a promising tool in regenerative medicine, especially wound healing and treatment of vascular disease.