title: Adenosine accelerates the healing of diabetic ischemic ulcers by improving autophagy of endothelial progenitor cells grown on a biomaterial.
abstract: Endothelial progenitor cells (EPCs) seeded on biomaterials can effectively promote diabetic ischemic wound healing. However, the function of transplanted EPCs is negatively affected by a high-glucose and ischemic microenvironment. Our experiments showed that EPC autophagy was inhibited and mitochondrial membrane potential (MMP) was increased in diabetic patients, while adenosine treatment decreased the energy requirements and increased the autophagy levels of EPCs. In animal experiments, we transplanted a biomaterial seeded with EPCs onto the surface of diabetic wounds and found that adenosine-stimulated EPCs effectively promoted wound healing. Increased microvascular genesis and survival of the transplanted cells were also observed in the adenosine-stimulated groups. Interestingly, our study showed that adenosine increased the autophagy of the transplanted EPCs seeded onto the biomaterial and maintained EPC survival at 48 and 96 hours. Moreover, we observed that adenosine induced EPC differentiation through increasing the level of autophagy. In conclusion, our study indicated that adenosine-stimulated EPCs seeded onto a biomaterial significantly improved wound healing in diabetic mice; mechanistically, adenosine might maintain EPC survival and differentiation by increasing high glucose-inhibited EPC autophagy and maintaining cellular energy metabolism.
authors.affiliation: Department of Anatomy, National&Regional Engineering Laboratory of Tissue Engineering, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Anatomy, National&Regional Engineering Laboratory of Tissue Engineering, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yangxiao
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Anatomy, National&Regional Engineering Laboratory of Tissue Engineering, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anatomy, National&Regional Engineering Laboratory of Tissue Engineering, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, China.
authors.forename: Mingcan
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Anatomy, Qiqihar Medical University, Qiqihar, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Anatomy, National&Regional Engineering Laboratory of Tissue Engineering, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Anatomy, National&Regional Engineering Laboratory of Tissue Engineering, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Anatomy, National&Regional Engineering Laboratory of Tissue Engineering, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Anatomy, National&Regional Engineering Laboratory of Tissue Engineering, Key Lab for Biomechanics and Tissue Engineering of Chongqing, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chuhong
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D001672:Biocompatible Materials; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000637:transplantation / Q000648:ultrastructure; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D033581:Stem Cell Transplantation / Q000379:methods; D014183:Transplantation, Heterologous; D014456:Ulcer / Q000503:physiopathology / Q000628:therapy*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001672:Biocompatible Materials; D000241:Adenosine