PMID- 30736851 OWN - NLM STAT- MEDLINE DCOM- 20190521 LR - 20200225 IS - 2047-783X (Electronic) IS - 0949-2321 (Print) IS - 0949-2321 (Linking) VI - 24 IP - 1 DP - 2019 Feb 8 TI - Human umbilical cord mesenchymal stem cells implantation accelerates cutaneous wound healing in diabetic rats via the Wnt signaling pathway. PG - 10 LID - 10.1186/s40001-019-0366-9 [doi] LID - 10 AB - OBJECTIVE: Difficulty in wound healing is one common complication of diabetes mellitus. The study explored whether the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic ulcer wound was enhanced by the activation of the Wnt signaling pathway. METHODS: Rat diabetic model was established by intraperitoneal injection of Streptozotocin (STZ). hUCMSCs were purified and seeded on the collagen-chitosan laser drilling acellular dermal matrix (CCLDADM) scaffold, which was subsequently implanted into the cutaneous wound of normal and diabetic rats, followed by daily injection of Wnt signaling pathway agonist (Wnt3a) or antagonist (sFRP3) at the edge of the scaffold. Wound healing was checked on days 7, 14, and 21, and the fibrous tissue deposition, capillaries, and epidermal regeneration at the wound were examined by hematoxylin-eosin staining. The hUCMSCs-CCLDADM scaffold was cultured in vitro and treated with Wnt3a or sFRP3, followed by evaluation of cell proliferation, cell proliferation rate, survival status, and altered protein levels in the Wnt signaling pathway using BrdU staining, CCK-8 assay, live/dead staining, and Western blotting, respectively. RESULTS: On days 7 and 14 postoperatively, the speed of wound healing was significantly lower in diabetic rats than that in normal control rats. This phenomenon was significantly improved by the activation of the Wnt signaling pathway that also elevated the fibrous protein deposition and the abundance of capillary in the granulation tissue. Conversely, blockade of Wnt signaling slowed the healing of skin wound in diabetic rats. The activation of Wnt signaling pathway promoted the proliferation and differentiation and decreased the apoptosis of hUCMSCs, thereby elevating the number of living hUCMSCs on the CCLDADM scaffold, while the suppression exerted a contrary effect. CONCLUSION: The activation of the Wnt signaling pathway promotes the healing of diabetic skin wound by the regulation of proliferation and differentiation of hUCMSCs on the CCLDADM scaffold. FAU - Han, Yanfu AU - Han Y AD - Department of Plastic Surgery, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyilu, Yangfangdian Haidian District, 100038, Beijing, People's Republic of China. FAU - Sun, Tianjun AU - Sun T AD - Department of Burn and Plastic Surgery, Hainan Branch of People's Liberation Army General Hospital, Haitangwan, Sanya, People's Republic of China. FAU - Han, Yanqing AU - Han Y AD - School of Electrical and Information Engineering, Wuhan Institute of Technology, 366 Huquan, Wuhan, People's Republic of China. FAU - Lin, Lingling AU - Lin L AD - Department of Burn and Plastic Surgery, Harrison International Peace Hospital, 180 Renmin East Road, Hengshui, Hebei, People's Republic of China. FAU - Liu, Chang AU - Liu C AD - Department of Plastic Surgery, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyilu, Yangfangdian Haidian District, 100038, Beijing, People's Republic of China. FAU - Liu, Jing AU - Liu J AD - Department of Plastic Surgery, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyilu, Yangfangdian Haidian District, 100038, Beijing, People's Republic of China. FAU - Yan, Guangzhi AU - Yan G AD - Department of Burn and Plastic Surgery, Harrison International Peace Hospital, 180 Renmin East Road, Hengshui, Hebei, People's Republic of China. yanguangzhi1234@126.com. FAU - Tao, Ran AU - Tao R AD - Department of Plastic Surgery, PLA General Hospital, 28 Fuxing Road, Beijing, People's Republic of China. lauruatr@163.com. LA - eng GR - No. Z1511000003150128/Beijing Nova Program/ GR - 2015SF45/Science and Technology Special Fund for Social Development of Hainan/ GR - 20181578/Hebei Province health and Family Planning Commission Research Fund Project/ PT - Journal Article DEP - 20190208 PL - England TA - Eur J Med Res JT - European journal of medical research JID - 9517857 SB - IM MH - Animals MH - Cell Differentiation/physiology MH - Cell Proliferation/physiology MH - Cord Blood Stem Cell Transplantation/*methods MH - *Diabetes Mellitus, Experimental MH - Heterografts MH - Humans MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Rats MH - Rats, Sprague-Dawley MH - Wnt Signaling Pathway/*physiology MH - Wound Healing/*physiology PMC - PMC6367839 OTO - NOTNLM OT - Diabetes mellitus OT - Mesenchymal stem cell therapy OT - Tissue engineering skin OT - Wnt signaling pathway OT - Wound healing EDAT- 2019/02/10 06:00 MHDA- 2019/05/22 06:00 PMCR- 2019/02/08 CRDT- 2019/02/10 06:00 PHST- 2018/08/12 00:00 [received] PHST- 2019/01/23 00:00 [accepted] PHST- 2019/02/10 06:00 [entrez] PHST- 2019/02/10 06:00 [pubmed] PHST- 2019/05/22 06:00 [medline] PHST- 2019/02/08 00:00 [pmc-release] AID - 10.1186/s40001-019-0366-9 [pii] AID - 366 [pii] AID - 10.1186/s40001-019-0366-9 [doi] PST - epublish SO - Eur J Med Res. 2019 Feb 8;24(1):10. doi: 10.1186/s40001-019-0366-9.