机构：[1]Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Institute of血管外科首都医科大学宣武医院[2]Department of Surgery, Yale School of Medicine, New Haven, CT, USA.[3]Department of Surgery, the First Hospital, China Medical University, Shenyang, China[4]Department of Surgery, VA Connecticut Healthcare System, West Haven, CT, USA.[5]Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT, USA
We have previously shown that bone marrow-derived mesenchymal stem cells (BMSC) accelerate wound healing in a diabetic mouse model. In this study, we hypothesized that adipose tissue-derived stem cells (ADSC), cells of greater translational potential to human therapy. improve diabetic wound healing to a similar extent as BMSC. In vitro, the characterization and function of murine ADSC and BMSC as well as human diabetic and nondiabetic ADSC were evaluated by flow cytometry, cell viability, and VEGE expression. In vivo. biomimetic collagen scaffolds containing murine ADSC or BMSC were used to treat splinted full-thickness excisional back wounds on diabetic C57BL/6 mice, and human healthy and diabetic ADSC were used to treat back wounds on nude mice. Wound healing was evaluated by wound area, local VEGF-A expression, and count of CD31-positive cells. Delivery of murine ADSC or BMSC accelerated wound healing in diabetic mice to a similar extent, compared with acellular controls (P < 0.0001). Histological analysis showed similarly increased cellular proliferation (P < 0.0001). VEGF-A expression (P = 0.0002), endothelial cell density (P < 0.0001). numbers of macrophages (P < 0.0001). and smooth muscle cells (P < 0.0001) with ADSC and BMSC treatment. compared with controls. Cell survival and migration of ADSC and BMSC within the scaffolds were similar (P = 0.781). Notch signaling was upregulated to a similar degree by both ADSC and BMSC. Diabetic and nondiabetic human ADSC expressed similar levels of VEGF-A (P = 0.836) in vitro, as well as in scaffolds (P = 1.000). Delivery of human diabetic and nondiabctic ADSC enhanced wound healing to a similar extent in a nude mouse wound model. Murine ADSC and BMSC delivered in a biomimetic-collagen scaffold are equivalent at enhancing diabetic wound healing. Human diabetic ADSC are not inferior to nondiabetic ADSC at accelerating wound healing in a nude mouse model. This data suggests that ADSC are a reasonable choice to evaluate for translational therapy in the treatment of human diabetic wounds.
基金：
This work was supported by the NIH Grant R01-HL128406 and by the
United States Department of Veterans 393 Affairs Biomedical Laboratory Research and Development Program, Merit Review Award I01-BX002336, Association of VA Surgeons Resident Research Award, as well as through the resources and use of facilities at the Veterans Affairs Connecticut Healthcare System (West Haven, CT).
第一作者机构：[1]Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Institute of[2]Department of Surgery, Yale School of Medicine, New Haven, CT, USA.[5]Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT, USA
共同第一作者：
通讯作者：
通讯机构：[*1]Yale University School of Medicine,10 Amistad Street, Room 437, PO Box 208089,New Haven, CT 06520-8089 USA.
推荐引用方式(GB/T 7714)：
Jianming Guo,Haidi Hu,Jolanta Gorecka,et al.Adipose-derived mesenchymal stem cells accelerate diabetic wound healing in a similar fashion as bone marrow-derived cells[J].AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY.2018,315(6):C885-C896.doi:10.1152/ajpcell.00120.2018.
APA：
Jianming Guo,Haidi Hu,Jolanta Gorecka,Hualong Bai,Hao He...&Alan Dardik.(2018).Adipose-derived mesenchymal stem cells accelerate diabetic wound healing in a similar fashion as bone marrow-derived cells.AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,315,(6)
MLA：
Jianming Guo,et al."Adipose-derived mesenchymal stem cells accelerate diabetic wound healing in a similar fashion as bone marrow-derived cells".AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 315..6(2018):C885-C896
