Exosomes from Adipose-Derived Stem Cells (ADSCs) Overexpressing miR-21 Promote Vascularization of Endothelial Cells

Abstract

In the past few years, exosomes released from adipose-derived stem cells (abbreviated as ADSCs) have shown promises to provide therapeutic benefits in the fields of regenerative medicine. miRNAs, existing in exosomes, are endogenous, small noncoding RNAs that play important roles in a variety of cellular functions and tumor development. Emerging evidences have indicated that miR-21 is one of the important miRNAs associated with tumor angiogenesis. In this study, we identified the role of exosomes from ADSCs overexpressing miR-21 in regulating/promoting vascularization of endothelial cells. Experimental data indicated an elevated miR-21 level in exosomes released by ADSCs overexpressing miR-21. In vitro matrigel angiogenesis assay showed that exosomes secreted by ADSCs overexpressing miR-21 significantly promoted the vascularization of HUVEC cells (an endothelial cell line). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) revealed an upregulation of HIF-1α, VEGF, SDF-1, p-Akt, p-ERK1/2 and downregulation of PTEN in response to miR-21 overexpression, indicating that miR-21 enriched exosomes induced angiogenesis through Akt and ERK activation and also HIF-1α and SDF-1 expression. Our work suggests that exosomes from ADSCs that overexpressing miR-21 can potentially promote vascularization and therefore the transplantation of exosomes from their culture may be suitable for clinical effort in regenerative medicine.

Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing

“…Others have confirmed the stimulation of ADSCs proliferation and keratinocytes chemoattraction via HIF-1α and VEGF, which are involved in angiogenesis and are facilitated by MMP [114,115]. Recently, SDF-1 has been released, together with HIF-1α in exosomes of ADSCs overexpressing miR-21, and potentially promotes angiogenesis [116]. Similar results were reported recently when using multiple injections of autologous ADSCs to burn wounds in the animal model, where angiogenesis was found to have an enhanced association with the increase in VEGF expression [78].…”

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

“…Yi et al (2019) reported that exosomes from osteocalcin-overexpressed EPCs showed a beneficial effect by stimulating the endothelial OCN-GPRC6A signaling. An et al (2019) reported that exosomes from ADSCs overexpressing miR-21 promote vascularization. Despite these beneficial effects, it is worthy to note that these genetic modifications of donor cells may also cause unwanted changes in exosomes.…”

microRNAs in Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Undergo Rapid Culture-Induced Changes in Expression, Including miR-378 which Promotes Adipogenesis

“…Microvesicle transport of miR-31 from ASC to endothelial cells has been shown to enhance angiogenesis [33]. It has also been recently shown that exosomes derived from murine ASC over-expressing miR-21 led to enhanced vascularisation of an endothelial cell line in vitro [34]. However, further studies are required to accurately determine the microRNA profile that is present in microvesicles derived from ex vivo ASC.…”