Extracellular vesicles derived from silicate‐stimulated antler reserve mesenchymal cells alleviate kidney damage in diabetic nephropathy through inhibiting abnormal angiogenesis and apoptosis

Abstract

Abstract Extracellular vesicles (EVs) facilitate the intercellular transfer of bioactive macromolecules and are capable of traversing physiological barriers and demonstrate considerable promise as innovative cell‐free therapies for treating a variety of diseases. Here, we showed a novel approach to use silicate ions (SiO 3 2− ) to stimulate secretion of high amounts of miR‐148a‐3p enriched extracellular vesicles (Si‐RM‐EVs) from antler reserve mesenchymal cells (RM cells). We further showed that the Si‐RM‐EVs were highly effective for the treatment of kidney damage in diabetic nephropathy (DN) mice with an enhanced ability to inhibit abnormal angiogenesis and apoptosis. We attribute the therapeutic effect to the high levels of bioactive miR‐148a‐3p in the EVs. Further in vitro experiments confirmed that miR‐148a‐3p overexpression suppressed angiogenesis and apoptosis of high‐glucose‐treated human umbilical vein endothelial cells (HUVEC) through inhibiting the expression of VEGFA and BCL2L11, and caused an increase in cell viability. Our study represented a new approach of using SiO 3 2− ‐antler RM cell‐based EV engineering for the treatment of kidney damage in DN and possibly in other tissue or organ damage.