title: Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair.
abstract: Split thickness skin graft (STSG) implantation is one of the standard therapies for full thickness wound repair when full thickness autologous skin grafts (FTG) or skin flap transplants are inapplicable. Combined transplantation of STSG with dermal substitute could enhance its therapeutic effects but the results remain unsatisfactory due to insufficient blood supply at early stages, which causes graft necrosis and fibrosis. Human mesenchymal stem cell (hMSC) sheets are capable of accelerating the wound healing process. We hypothesized that pre-vascularized hMSC sheets would further improve regeneration by providing more versatile angiogenic factors and pre-formed microvessels. In this work,in vitrocultured hMSC cell sheets (HCS) and pre-vascularized hMSC cell sheets (PHCS) were implanted in a rat full thickness skin wound model covered with an autologous STSG. Results demonstrated that the HCS and the PHCS implantations significantly reduced skin contraction and improved cosmetic appearance relative to the STSG control group. The PHCS group experienced the least hemorrhage and necrosis, and lowest inflammatory cell infiltration. It also induced the highest neovascularization in early stages, which established a robust blood micro-circulation to support grafts survival and tissue regeneration. Moreover, the PHCS grafts preserved the largest amount of skin appendages, including hair follicles and sebaceous glands, and developed the smallest epidermal thickness. The superior therapeutic effects seen in PHCS groups were attributed to the elevated presence of growth factors and cytokines in the pre-vascularized cell sheet, which exerted a beneficial paracrine signaling during wound repair. Hence, the strategy of combining STSG with PHCS implantation appears to be a promising approach in regenerative treatment of full thickness skin wounds.
authors.affiliation: Department of Burns, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University, Houghton, Michigan, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Department of Burns, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Qiyi
authors.initials: Q
authors.lastname: Zhai
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University, Houghton, Michigan, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Tahtinen
authors.affiliation: Department of Burns, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Pathology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Burns, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Burns, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Shaohai
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University, Houghton, Michigan, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
mesh_terms: D000818:Animals; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D018919:Neovascularization, Physiologic; D051381:Rats; D012867:Skin / Q000033:anatomy & histology; D016038:Skin Transplantation / Q000379:methods*; D045506:Therapeutic Uses; D014947:Wounds and Injuries / Q000628:therapy*
chemical_list: D045506:Therapeutic Uses
keywords: angiogenic growth factors; human mesenchymal stem cell; prevascularized cell sheet; skin graft