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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 vitro cultured 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.

SUBMITTER: Chen L

PROVIDER: S-EPMC5196890 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair.

Chen Lei L Xing Qi Q Zhai Qiyi Q Tahtinen Mitchell M Zhou Fei F Chen Lili L Xu Yingbin Y Qi Shaohai S Zhao Feng F

Theranostics 20170101 1

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 th ...[more]

PMID: 28042321

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Project description:BackgroundFull thickness burn wounds are lack of angiogenesis, cell migration, epithelialisation and finally scar tissue formation. Tissue engineered composite graft can provide sustained release of growth factor and promote the wound healing by cell migration, early angiogenesis and proliferation of extracellular matrix and wound remodeling. The objective of this study was to evaluate the gene embedded (pDNA-platelet-derived growth factor, PDGF-B) porcine acellular urinary bladder matrix with transfected mesenchymal stem cells (rBMSC) on healing of full thickness burn wound in rat model.MethodsFull thickness burn wound of 2 × 2 cm size was created in dorsum of rat model under general anesthesia. Burn wounds were treated with silver sulfadiazine; porcine acellular urinary bladder matrix (PAUBM); PAUBM transfected with pDNA-PDGF-B; PAUBM seeded with rBMSC; PAUBM seeded with rBMSC transfected with pDNA-PDGF-B in groups A, B, C, D and E respectively. The wound healing was assessed based on clinical, macroscopically, immunologically, histopathological and RT-qPCR parameters.ResultsWound was significantly healed in group E and group D with early extracellular matrix deposition, enhanced granulation tissue formation and early angiogenesis compared to all other groups. The immunologic response against porcine acellular matrix showed that PDGF-B gene activated matrix along with stem cell group showed less antibody titer against acellular matrix than other groups in all intervals. PDGF gene activated matrix releasing the PDGF-B and promote the healing of full thickness burn wound with neovascularization and neo tissue formation. PDGF gene also enhances secretion of other growth factors results in PDGF mediated regenerative activities. This was confirmed in RT-qPCR at various time intervals.ConclusionGene activated matrix encoded for PDGF-B protein transfected stem cells have been clinically proven for early acceleration of angiogenesis and tissue regeneration in burn wounds in rat models. Evaluation of PDGF-B gene-activated acellular matrix and mesenchymal stem cell in full thickness skin burn wound in rat.

Project description:BackgroundWound healing involves the integration of complex biological processes. Several studies examined numerous approaches to enhance wound healing and to minimize its related morbidity. Both chitosan and mesenchymal stem cells (MSCs) were used in treating skin wounds. The aim of the current work was to compare MSCs versus chitosan in wound healing, evaluate the most efficient route of administration of MSCs, either intradermal or systemic injection, and elicit the mechanisms inducing epidermal and dermal cell regeneration using histological, immunohistochemical and fluorescent techniques.Material and methodsForty adult male Sprague Dawley albino rats were divided into four equal groups (ten rats in each group): control group (Group I); full thickness surgical skin wound model, Group II: Wound and chitosan gel. Group III: Wound treated with systemic injection of MSCs and Group IV: Wound treated with intradermal injection of MSCs. The healing ulcer was examined on day 3, 5, 10 and 15 for gross morphological evaluation and on day 10 and 15 for histological, immunohistochemical and fluorescent studies.ResultsChitosan was proved to promote wound healing more than the control group but none of their wound reached complete closure. Better and faster healing of wounds in MSCs treated groups were manifested more than the control or chitosan treated groups. It was found that the intradermal route of administration of stem cells enhanced the rate of healing of skin wounds better than the systemic administration to the extent that, by the end of the fifteenth day of the experiment, the wounds were completely healed in all rats of this group. Histologically, the wound areas of group IV were hardly demarcated from the adjacent normal skin and showed complete regeneration of the epidermis, dermis, hypodermis and underlying muscle fibers. Collagen fibers were arranged in many directions, with significant increase in their area percent, surrounding fully regenerated hair follicles and sebaceous glands in the dermis of the healed areas more than in other groups.ConclusionMSCs enhanced the healing process of wound closure more than chitosan gel treatment. Furthermore, MSCs injected intradermally, were more efficient in accelerating wound healing than any other mode of treatment.

Dataset Information

Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair.

Publications

Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair.

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