The effect of heme oxygenase-1 complexed with collagen on MSC performance in the treatment of diabetic ischemic ulcer.
Diabetic ischemic ulcer is an intractable diabetic complication. Bone marrow mesenchymal stem cells (BMSCs) have great potential in variety of tissue repair. In fact, poor cell viability and tolerance limit their ability for tissue repair. In addition, it is difficult for stem cells to home and locate to the lesion. In this study, we explore whether over-expression of heme oxygenase-1 (HO-1) in BMSCs complexed with collagen play an important role in treatment of diabetic ischemic ulcers. In vitro, over-expression of HO-1 promoted the proliferation and paracrine activity of BMSCs and the conditioned medium of BMSCs accelerated HUVECs migration and proliferation. These processes were closely related to Akt signaling pathway and were not dependent on Erk signaling pathway. In vivo, in order to make BMSCs directly act on the wound, we choose a solid collagen as a carrier, BMSCs were planted into it, ischemic wounds of diabetic mice were covered with the complex of BMSCs and collagen. The results indicate that the complex of HO-1-overexpressing BMSCs and collagen biomaterials can significantly promote angiogenesis and wound healing. These preclinical findings open new perspectives for the treatment of diabetic foot ulcers.
Department of Anatomy, Key Lab of Biomechanics, Third Military Medical University, Chongqing 400038, China.
Chunli
C
Hou
Lei
L
Shen
Qiang
Q
Huang
Jianhong
J
Mi
Yangxiao
Y
Wu
Mingcan
M
Yang
Wen
W
Zeng
Li
L
Li
Wen
W
Chen
Chuhong
C
Zhu
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology / Q000628:therapy*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000150:complications / Q000473:pathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019899:Paracrine Communication / Q000187:drug effects; D011524:Protoporphyrins / Q000494:pharmacology; D014456:Ulcer / Q000150:complications / Q000473:pathology / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D001672:Biocompatible Materials; D017077:Culture Media, Conditioned; D008665:Metalloporphyrins; D011524:Protoporphyrins; D042461:Vascular Endothelial Growth Factor A; C007095:cobaltiprotoporphyrin; D003094:Collagen; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1