Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis

Abstract

Background Enhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing. Results We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing. Conclusions PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing. Graphic abstract

Hemin enhances the cardioprotective effects of mesenchymal stem cell-derived exosomes against infarction via amelioration of cardiomyocyte senescence

“…MSC-EXO exert beneficial effects via bioactive substances that include proteins, mRNAs, LncRNA and miRNAs. Notably, the substances in MSC-EXO are largely influenced by environmental stimuli that alters their biological effect [ 20 , 21 ]. Thus, optimizing MSC-EXO in vitro to enhance their therapeutic effects is of great importance.…”

Rat Bone Mesenchymal Stem Cell‐Derived Exosomes Loaded with miR‐494 Promoting Neurofilament Regeneration and Behavioral Function Recovery after Spinal Cord Injury

“…Exos are small membrane vesicles originating from intracellular corpuscles, exhibiting a diameter of about 30–200 nm, which are packed with various proteins, lipids, and RNA. These vesicles can be released into extracellular fluid, blood, and cerebrospinal fluid by cells of all living systems [ 5 , 6 ]. Under physiological and pathophysiological conditions, they are capable of transferring their cargo between source cells and target cells via extracellular fluid, blood, and cerebrospinal fluid, and they critically impact intercellular communication [ 7 ].…”

Exosomes Derived from Bone Mesenchymal Stem Cells Alleviate Compression‐Induced Nucleus Pulposus Cell Apoptosis by Inhibiting Oxidative Stress

“…Recent studies displayed that exosomes are a treatment modality that may offer a promising therapeutic strategy for tissue regeneration [ 32 , 33 ]. Exosomes have received extensive attention because they were reported to possess functional proteins and miRNAs that have many positive impacts in mediating cellular function and treating a variety of diseases [ 16 , 34 , 35 ]. Recent studies indicated that MSCs-Exos protect endplate chondrocytes against death and offer a potential strategy for IVD degeneration [ 36 ].…”

“…This study was approved by the Clinical Research Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. According to our previous research, SD rats were isolated BMSCs [ 16 , 23 ]. Briefly, the bone marrow of the femur and tibia was washed with a syringe.…”

“…Interestingly, evidence from prior studies indicated that stem cells can serve their tissue repair function through paracrine exosomes. Exosomes, microvesicles with a diameter between 30 and 150 nm, can deliver growth factors, and proteins to target cells and exert their function [ 16 , 17 ]. Exosomes have many advantages compared to MSCs, including greater stability and low immunogenicity [ 18 – 20 ].…”