miR-21 has been indicated to be an important regulator of angiogenesis, involving in regulating the proliferation and migration of vascular cells, like endothelial cells.
Direct evidences have shown that downregulation of miR-21 expression signifcantly reduces the proliferation and migration of HUVECs, and conversely, miR-21 overexpression signifcantly enhances HUVECs proliferation and migration, indicating the importance of miR21 on angiogenesis.
In spite that miR-21, as a circulating tumor biomarker, exerts its efect at multiple steps in cancer metastasis by afecting adhesion, migration, invasion, and angiogenesis, we are still able to make the most utilization of it for therapeutic purpose by integrating its function with ADSC exosomes.
Here we used exosomes from ADSCs in combination with miR-21 overexpression to promote the vascularization of endothelial cells for regenerative purpose and demonstrated that miR-21 induces tumor angiogenesis through targeting PTEN, leading to activate AKT and ERK1/2 signaling pathways, and thereby enhancing HIF-1α and VEGF expression.
Results demonstrate that exosomes secreted by ADSCs overexpressing miR-21 could possibly be used to assist wound healing by improving vascularization.
Exosome therapy in combination with onco-miRs may represents a multi-faceted, paradigm-shif strategy for promoting regenerative tissue engineering and carry huge expectations for medical and clinical application in the near future.