Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia
نویسندگان
چکیده
Abstract Background Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty differentiation, tumorigenicity transplanted restricted its application. Recent studies have found exosomes secreted by ADSCs advantages containing parental beneficial factors exhibiting non-immunogenic, non-tumorigenic, strong stable characteristics. Methods GLO-1 (G-ADSCs) were established using lentivirus transfection, from (G-ADSC-Exos) isolated characterized coculture with human umbilical vein endothelial (HUVECs). Proliferation, apoptosis, migration, tube formation HUVECs detected under high-glucose conditions. The G-ADSC-Exos injected into hindlimb muscles type 2 diabetes mellitus (T2DM) laser Doppler perfusion index, Masson’s staining, immunofluorescence, immunohistochemistry assays adopted assess treatment efficiency. Moreover, underlying regulatory mechanisms on proliferation, angiogenesis, apoptosis explored. Results enhanced formation, anti-apoptosis vitro After vivo transplantation, G-ADSC-Exo group showed significantly higher better muscle structural integrity, microvessel’s density than ADSC-Exo control groups staining immunofluorescence assays. which protected both might be via activation eNOS/AKT/ERK/P-38 signaling pathways, inhibition AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1β, as well increased secretion VEGF, IGF-1, FGF. Conclusion Exosomes derived angiogenesis mice ischemia, will promising ischemia.
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ژورنال
عنوان ژورنال: Stem Cell Research & Therapy
سال: 2021
ISSN: ['1757-6512']
DOI: https://doi.org/10.1186/s13287-021-02475-7