PMID- 36840468 OWN - NLM STAT- MEDLINE DCOM- 20230228 LR - 20240130 IS - 1555-3892 (Electronic) IS - 0963-6897 (Print) IS - 0963-6897 (Linking) VI - 32 DP - 2023 Jan-Dec TI - In Situ-Formed Fibrin Hydrogel Scaffold Loaded With Human Umbilical Cord Mesenchymal Stem Cells Promotes Skin Wound Healing. PG - 9636897231156215 LID - 10.1177/09636897231156215 [doi] LID - 09636897231156215 AB - Healing of full-thickness skin wounds remains a major challenge. Recently, human umbilical cord mesenchymal stem cells (hUC-MSCs) were shown to possess an extraordinary potential to promote skin repair in clinical settings. However, their low survival rate after transplantation limits their therapeutic efficiency in treating full-thickness skin wounds. Hydrogels are considered an ideal cell transplantation vector owing to their three-dimensional mesh structure, good biosafety, and biodegradation. The objective of this study was to investigate the skin wound healing effect of a fibrin hydrogel scaffold loaded with hUC-MSCs. We found that the fibrin hydrogel had a three-dimensional mesh structure and low cytotoxicity and could prolong the time of cell survival in the peri-wound area. The number of green fluorescent protein (GFP)-labeled hUC-MSCs was higher in the full-thickness skin wound of mice treated with hydrogel-hUC-MSCs than those of mice treated with cell monotherapy. In addition, the combination therapy between the hydrogel and hUC-MSCs speed up wound closure, its wound healing rate was significantly higher than those of phosphate-buffered saline (PBS) therapy, hydrogel monotherapy, and hUC-MSCs monotherapy. Furthermore, the results showed that the combination therapy between hydrogel and hUC-MSCs increased keratin 10 and keratin 14 immunofluorescence staining, and upregulated the relative gene expressions of epidermal growth factor (EGF), transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor A (VEGFA), promoting epithelial regeneration and angiogenesis. In conclusion, the fibrin hydrogel scaffold provides a relatively stable sterile environment for cell adhesion, proliferation, and migration, and prolongs cell survival at the wound site. The hydrogel-hUC-MSCs combination therapy promotes wound closure, re-epithelialization, and neovascularization. It exhibits a remarkable therapeutic effect, being more effective than the monotherapy with hUC-MSCs or hydrogel. FAU - Hu, Lvzhong AU - Hu L AUID- ORCID: 0000-0002-2760-8871 AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Zhou, Jinhua AU - Zhou J AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China. FAU - He, Zhisong AU - He Z AD - Department of Cardiovascular Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Zhang, Lin AU - Zhang L AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Du, Fangzhou AU - Du F AD - Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China. FAU - Nie, Mengting AU - Nie M AD - Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China. AD - School of Life Science and Technology, Changchun University of Science and Technology, Changchun, China. FAU - Zhou, Yao AU - Zhou Y AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Hao, Hang AU - Hao H AD - Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China. FAU - Zhang, Lixing AU - Zhang L AD - Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China. FAU - Yu, Shuang AU - Yu S AD - Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China. AD - Zhengzhou Institute of Engineering and Technology Affiliated to SIBET, Zhengzhou, China. AD - Xuzhou Medical University, Xuzhou, China. FAU - Zhang, Jingzhong AU - Zhang J AD - Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China. AD - Zhengzhou Institute of Engineering and Technology Affiliated to SIBET, Zhengzhou, China. AD - Xuzhou Medical University, Xuzhou, China. FAU - Chen, Youguo AU - Chen Y AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 RN - 0 (Hydrogels) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Animals MH - Humans MH - Mice MH - Hydrogels MH - *Mesenchymal Stem Cell Transplantation/methods MH - *Mesenchymal Stem Cells MH - Umbilical Cord/cytology MH - Vascular Endothelial Growth Factor A/metabolism MH - *Wound Healing MH - Tissue Scaffolds PMC - PMC9969468 OTO - NOTNLM OT - fibrin OT - human umbilical cord mesenchymal stem cells OT - hydrogel OT - skin wound healing COIS- The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2023/02/26 06:00 MHDA- 2023/03/03 06:00 PMCR- 2023/02/25 CRDT- 2023/02/25 04:53 PHST- 2023/02/25 04:53 [entrez] PHST- 2023/02/26 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/02/25 00:00 [pmc-release] AID - 10.1177_09636897231156215 [pii] AID - 10.1177/09636897231156215 [doi] PST - ppublish SO - Cell Transplant. 2023 Jan-Dec;32:9636897231156215. doi: 10.1177/09636897231156215.