An ADSC-loaded dermal regeneration template promotes full-thickness wound healing

Introduction: Full-thickness wounds lead to delayed wound healing and scarring. Adipose-derived stem cell (ADSC) grafting promotes wound healing and minimizes scarring, but the low efficiency of grafting has been a challenge. We hypothesized that loading ADSCs onto a clinically widely used dermal re...

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Main Authors: Jin Xu, Xuelian Chen, Jizhuang Wang, Beibei Zhang, Wenjia Ge, Jiaqiang Wang, Peilang Yang, Yan Liu
Format: Article
Language:English
Published: Elsevier 2024-06-01
Series:Regenerative Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352320424001470
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author Jin Xu
Xuelian Chen
Jizhuang Wang
Beibei Zhang
Wenjia Ge
Jiaqiang Wang
Peilang Yang
Yan Liu
author_facet Jin Xu
Xuelian Chen
Jizhuang Wang
Beibei Zhang
Wenjia Ge
Jiaqiang Wang
Peilang Yang
Yan Liu
author_sort Jin Xu
collection DOAJ
description Introduction: Full-thickness wounds lead to delayed wound healing and scarring. Adipose-derived stem cell (ADSC) grafting promotes wound healing and minimizes scarring, but the low efficiency of grafting has been a challenge. We hypothesized that loading ADSCs onto a clinically widely used dermal regeneration template (DRT) would improve the efficacy of ADSC grafting and promote full-thickness wound healing. Methods: ADSCs from human adipose tissue were isolated, expanded, and labeled with a cell tracker. Labeled ADSCs were loaded onto the DRT. The viability, the location of ADSCs on the DRT, and the abundance of ADSCs in the wound area were confirmed using CCK8 and fluorescence microscopy. Full-thickness wounds were created on Bama minipigs, which were applied with sham, ADSC, DRT, and ADSC-DRT. Wounds from the four groups were collected at the indicated time and histological analysis was performed. RNA-seq analysis was also conducted to identify transcriptional differences among the four groups. The identified genes by RNA-seq were verified by qPCR. Immunohistochemistry and western blotting were used to assess collagen deposition. In vitro, the supernatant of ADSCs was used to culture fibroblasts to investigate the effect of ADSCs on fibroblast transformation into myofibroblasts. Results: ADSCs were successfully isolated, marked, and loaded onto the DRT. The abundance of ADSCs in the wound area was significantly greater in the ADSC-DRT group than in the ADSC group. Moreover, the ADSC-DRT group exhibited better wound healing with improved re-epithelialization and denser collagen deposition than the other three groups. The RNA-seq results suggested that the application of the integrated ADSC-DRT system resulted in the differential expression of genes mainly associated with extracellular matrix remodeling. In vivo, wounds from the ADSC-DRT group exhibited an earlier increase in type III collagen deposition and alleviated scar formation. ADSCs inhibited the transformation of fibroblasts into myofibroblasts, along with increased levels of CTGF, FGF, and HGF in the supernatant of ADSCs. Wounds from the ADSC-DRT group had up-regulated expressions of CTGF, HGF, FGF, and MMP3. Conclusion: The integral of ADSC-DRT increased the efficacy of ADSC grafting, and promoted full-thickness wound healing with better extracellular matrix remodeling and alleviated scar formation.
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spelling doaj-art-ea29355e24d84493b2ab5e96d7c989812024-11-30T07:10:56ZengElsevierRegenerative Therapy2352-32042024-06-0126800810An ADSC-loaded dermal regeneration template promotes full-thickness wound healingJin Xu0Xuelian Chen1Jizhuang Wang2Beibei Zhang3Wenjia Ge4Jiaqiang Wang5Peilang Yang6Yan Liu7Department of Burn, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Plastic Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Burn, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Burn, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Plastic Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Plastic Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Burn, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Burn, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author.Department of Burn, Ruijin Hospital, Shanghai Burn Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author.Introduction: Full-thickness wounds lead to delayed wound healing and scarring. Adipose-derived stem cell (ADSC) grafting promotes wound healing and minimizes scarring, but the low efficiency of grafting has been a challenge. We hypothesized that loading ADSCs onto a clinically widely used dermal regeneration template (DRT) would improve the efficacy of ADSC grafting and promote full-thickness wound healing. Methods: ADSCs from human adipose tissue were isolated, expanded, and labeled with a cell tracker. Labeled ADSCs were loaded onto the DRT. The viability, the location of ADSCs on the DRT, and the abundance of ADSCs in the wound area were confirmed using CCK8 and fluorescence microscopy. Full-thickness wounds were created on Bama minipigs, which were applied with sham, ADSC, DRT, and ADSC-DRT. Wounds from the four groups were collected at the indicated time and histological analysis was performed. RNA-seq analysis was also conducted to identify transcriptional differences among the four groups. The identified genes by RNA-seq were verified by qPCR. Immunohistochemistry and western blotting were used to assess collagen deposition. In vitro, the supernatant of ADSCs was used to culture fibroblasts to investigate the effect of ADSCs on fibroblast transformation into myofibroblasts. Results: ADSCs were successfully isolated, marked, and loaded onto the DRT. The abundance of ADSCs in the wound area was significantly greater in the ADSC-DRT group than in the ADSC group. Moreover, the ADSC-DRT group exhibited better wound healing with improved re-epithelialization and denser collagen deposition than the other three groups. The RNA-seq results suggested that the application of the integrated ADSC-DRT system resulted in the differential expression of genes mainly associated with extracellular matrix remodeling. In vivo, wounds from the ADSC-DRT group exhibited an earlier increase in type III collagen deposition and alleviated scar formation. ADSCs inhibited the transformation of fibroblasts into myofibroblasts, along with increased levels of CTGF, FGF, and HGF in the supernatant of ADSCs. Wounds from the ADSC-DRT group had up-regulated expressions of CTGF, HGF, FGF, and MMP3. Conclusion: The integral of ADSC-DRT increased the efficacy of ADSC grafting, and promoted full-thickness wound healing with better extracellular matrix remodeling and alleviated scar formation.http://www.sciencedirect.com/science/article/pii/S2352320424001470Adipose-derived stem cellsDermal regeneration templateFull-thickness wounds
spellingShingle Jin Xu
Xuelian Chen
Jizhuang Wang
Beibei Zhang
Wenjia Ge
Jiaqiang Wang
Peilang Yang
Yan Liu
An ADSC-loaded dermal regeneration template promotes full-thickness wound healing
Regenerative Therapy
Adipose-derived stem cells
Dermal regeneration template
Full-thickness wounds
title An ADSC-loaded dermal regeneration template promotes full-thickness wound healing
title_full An ADSC-loaded dermal regeneration template promotes full-thickness wound healing
title_fullStr An ADSC-loaded dermal regeneration template promotes full-thickness wound healing
title_full_unstemmed An ADSC-loaded dermal regeneration template promotes full-thickness wound healing
title_short An ADSC-loaded dermal regeneration template promotes full-thickness wound healing
title_sort adsc loaded dermal regeneration template promotes full thickness wound healing
topic Adipose-derived stem cells
Dermal regeneration template
Full-thickness wounds
url http://www.sciencedirect.com/science/article/pii/S2352320424001470
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