Dedifferentiated fat cells-derived exosomes (DFATs-Exos) loaded in GelMA accelerated diabetic wound healing through Wnt/β-catenin pathway

Abstract Background Diabetic foot ulcers pose significant challenges for clinicians worldwide. Cell-free exosome therapy holds great potential for wound healing. Dedifferentiated fat cells (DFATs) have been used in tissue engineering and regeneration, but there are no reports on the use of DFATs-der...

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Main Authors: Miao Dong, Xuan Ma, Facheng Li
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-025-04205-9
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author Miao Dong
Xuan Ma
Facheng Li
author_facet Miao Dong
Xuan Ma
Facheng Li
author_sort Miao Dong
collection DOAJ
description Abstract Background Diabetic foot ulcers pose significant challenges for clinicians worldwide. Cell-free exosome therapy holds great potential for wound healing. Dedifferentiated fat cells (DFATs) have been used in tissue engineering and regeneration, but there are no reports on the use of DFATs-derived exosomes in diabetic wound repair. Objectives This study aims to investigate whether DFATs-Exos accelerated diabetic wound healing and explore its potential mechanism. Methods In vitro, DFATs-Exos were harvested from adipose tissue and used to treat endothelial cells (ECs) and fibroblasts. XAV939 was used as a Wnt/β-catenin pathway inhibitor. The biocompatibility of gelatin methacryloyl (GelMA) hydrogel was assessed. In vivo, DFAT-derived exosomes were encapsulated in 10% GelMA hydrogel and applied to a diabetic wound model. Histological analysis and wound closure rates were evaluated. Results DFATs-Exos promoted angiogenesis in ECs and significantly alleviated the high glucose-induced inhibition of cell proliferation and migration by activating the Wnt/β-catenin pathway. In vivo, compared to DFAT-Exos or GelMA alone, the DFAT-Exos/GelMA combination accelerated wound closure and enhanced collagen maturity. Conclusion The DFAT-Exos/GelMA hydrogel significantly promoted wound healing in a diabetic animal model through activation of the Wnt/β-catenin signaling pathway.
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spelling doaj-art-19e7f866d7ab43539052a1a4fbc175a22025-08-20T03:04:27ZengBMCStem Cell Research & Therapy1757-65122025-02-0116111710.1186/s13287-025-04205-9Dedifferentiated fat cells-derived exosomes (DFATs-Exos) loaded in GelMA accelerated diabetic wound healing through Wnt/β-catenin pathwayMiao Dong0Xuan Ma1Facheng Li2Department of Body Contouring and Fat grafting Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Body Contouring and Fat grafting Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Body Contouring and Fat grafting Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background Diabetic foot ulcers pose significant challenges for clinicians worldwide. Cell-free exosome therapy holds great potential for wound healing. Dedifferentiated fat cells (DFATs) have been used in tissue engineering and regeneration, but there are no reports on the use of DFATs-derived exosomes in diabetic wound repair. Objectives This study aims to investigate whether DFATs-Exos accelerated diabetic wound healing and explore its potential mechanism. Methods In vitro, DFATs-Exos were harvested from adipose tissue and used to treat endothelial cells (ECs) and fibroblasts. XAV939 was used as a Wnt/β-catenin pathway inhibitor. The biocompatibility of gelatin methacryloyl (GelMA) hydrogel was assessed. In vivo, DFAT-derived exosomes were encapsulated in 10% GelMA hydrogel and applied to a diabetic wound model. Histological analysis and wound closure rates were evaluated. Results DFATs-Exos promoted angiogenesis in ECs and significantly alleviated the high glucose-induced inhibition of cell proliferation and migration by activating the Wnt/β-catenin pathway. In vivo, compared to DFAT-Exos or GelMA alone, the DFAT-Exos/GelMA combination accelerated wound closure and enhanced collagen maturity. Conclusion The DFAT-Exos/GelMA hydrogel significantly promoted wound healing in a diabetic animal model through activation of the Wnt/β-catenin signaling pathway.https://doi.org/10.1186/s13287-025-04205-9Diabetic wound healingDedifferentiated fat cellsExosomesGelMA hydrogelWnt / β-catenin pathway
spellingShingle Miao Dong
Xuan Ma
Facheng Li
Dedifferentiated fat cells-derived exosomes (DFATs-Exos) loaded in GelMA accelerated diabetic wound healing through Wnt/β-catenin pathway
Stem Cell Research & Therapy
Diabetic wound healing
Dedifferentiated fat cells
Exosomes
GelMA hydrogel
Wnt / β-catenin pathway
title Dedifferentiated fat cells-derived exosomes (DFATs-Exos) loaded in GelMA accelerated diabetic wound healing through Wnt/β-catenin pathway
title_full Dedifferentiated fat cells-derived exosomes (DFATs-Exos) loaded in GelMA accelerated diabetic wound healing through Wnt/β-catenin pathway
title_fullStr Dedifferentiated fat cells-derived exosomes (DFATs-Exos) loaded in GelMA accelerated diabetic wound healing through Wnt/β-catenin pathway
title_full_unstemmed Dedifferentiated fat cells-derived exosomes (DFATs-Exos) loaded in GelMA accelerated diabetic wound healing through Wnt/β-catenin pathway
title_short Dedifferentiated fat cells-derived exosomes (DFATs-Exos) loaded in GelMA accelerated diabetic wound healing through Wnt/β-catenin pathway
title_sort dedifferentiated fat cells derived exosomes dfats exos loaded in gelma accelerated diabetic wound healing through wnt β catenin pathway
topic Diabetic wound healing
Dedifferentiated fat cells
Exosomes
GelMA hydrogel
Wnt / β-catenin pathway
url https://doi.org/10.1186/s13287-025-04205-9
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AT xuanma dedifferentiatedfatcellsderivedexosomesdfatsexosloadedingelmaaccelerateddiabeticwoundhealingthroughwntbcateninpathway
AT fachengli dedifferentiatedfatcellsderivedexosomesdfatsexosloadedingelmaaccelerateddiabeticwoundhealingthroughwntbcateninpathway