Constructing Tissue-Engineered Dressing Membranes with Adipose-Derived Stem Cells and Acellular Dermal Matrix for Diabetic Wound Healing: A Comparative Study of Hypoxia- or Normoxia-Culture Modes

Diabetes foot ulcer (DFU) is a serious complication of diabetes, characterized by impaired vascular function, limited angiogenesis, and chronic inflammation. Direct stem cell injection on treating DFU is far from satisfactory in clinical practice, as this therapy neither protects nor localizes the i...

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Main Authors: Wen Zhou, Xin Zhao, Xin Shi, Can Chen, Yanpeng Cao, Jun Liu
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2022/2976185
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author Wen Zhou
Xin Zhao
Xin Shi
Can Chen
Yanpeng Cao
Jun Liu
author_facet Wen Zhou
Xin Zhao
Xin Shi
Can Chen
Yanpeng Cao
Jun Liu
author_sort Wen Zhou
collection DOAJ
description Diabetes foot ulcer (DFU) is a serious complication of diabetes, characterized by impaired vascular function, limited angiogenesis, and chronic inflammation. Direct stem cell injection on treating DFU is far from satisfactory in clinical practice, as this therapy neither protects nor localizes the injected cell suspension at the chronic ulcer site. Meanwhile, most of injected cells gradually perished within several days due to senescence or apoptosis. Acellular dermal matrix (ADM) has the potential to act as excellent cell delivery vehicles, considering it is highly biomimetic to native dermal tissue, has low immunogenicity, and suitable for stem cell attachment and proliferation. Hypoxia culture has significantly enhanced effects on the survival ability of in vitro cultured stem cells, indicating this culture mode is a suitable way for inhibiting the senescence or apoptosis of transplanted cells. In the current study, we, respectively, culture adipose-derived stem cells (ADSCs) on an ADM membrane under a hypoxia or normoxia condition to construct two kinds of tissue-engineered dressing membranes (H-ADSCs/ADM and N-ADSCs/ADM) and then comparatively evaluated their efficacy on DFU healing using a diabetic rat model. In vitro results showed that hypoxia precondition could stimulate the ADSCs secreting VEGF-A, and the culture medium from hypoxia-preconditioned ADSCs could enhance the proliferation, migration, and angiogenesis of HUVECs. In vivo results indicated that compared to the N-ADSCs/ADM membrane, the transplanted cells in the H-ADSCs/ADM membrane can survive longer at the chronic ulcer site, consequently improve angiogenesis, inhibit inflammation, and increase extracellular matrix remodeling, eventually accelerating DFU closure. This study provides an innovative covering graft for the treatment of DFU in the clinic.
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spelling doaj-art-dd358035199d4f3293986cee1a56048a2025-02-03T01:22:27ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/2976185Constructing Tissue-Engineered Dressing Membranes with Adipose-Derived Stem Cells and Acellular Dermal Matrix for Diabetic Wound Healing: A Comparative Study of Hypoxia- or Normoxia-Culture ModesWen Zhou0Xin Zhao1Xin Shi2Can Chen3Yanpeng Cao4Jun Liu5Clinical Nursing Teaching and Research SectionDepartment of Limbs (Foot and Hand) MicrosurgeryThe First School of Clinical MedicineDepartment of OrthopedicsDepartment of Limbs (Foot and Hand) MicrosurgeryDepartment of Limbs (Foot and Hand) MicrosurgeryDiabetes foot ulcer (DFU) is a serious complication of diabetes, characterized by impaired vascular function, limited angiogenesis, and chronic inflammation. Direct stem cell injection on treating DFU is far from satisfactory in clinical practice, as this therapy neither protects nor localizes the injected cell suspension at the chronic ulcer site. Meanwhile, most of injected cells gradually perished within several days due to senescence or apoptosis. Acellular dermal matrix (ADM) has the potential to act as excellent cell delivery vehicles, considering it is highly biomimetic to native dermal tissue, has low immunogenicity, and suitable for stem cell attachment and proliferation. Hypoxia culture has significantly enhanced effects on the survival ability of in vitro cultured stem cells, indicating this culture mode is a suitable way for inhibiting the senescence or apoptosis of transplanted cells. In the current study, we, respectively, culture adipose-derived stem cells (ADSCs) on an ADM membrane under a hypoxia or normoxia condition to construct two kinds of tissue-engineered dressing membranes (H-ADSCs/ADM and N-ADSCs/ADM) and then comparatively evaluated their efficacy on DFU healing using a diabetic rat model. In vitro results showed that hypoxia precondition could stimulate the ADSCs secreting VEGF-A, and the culture medium from hypoxia-preconditioned ADSCs could enhance the proliferation, migration, and angiogenesis of HUVECs. In vivo results indicated that compared to the N-ADSCs/ADM membrane, the transplanted cells in the H-ADSCs/ADM membrane can survive longer at the chronic ulcer site, consequently improve angiogenesis, inhibit inflammation, and increase extracellular matrix remodeling, eventually accelerating DFU closure. This study provides an innovative covering graft for the treatment of DFU in the clinic.http://dx.doi.org/10.1155/2022/2976185
spellingShingle Wen Zhou
Xin Zhao
Xin Shi
Can Chen
Yanpeng Cao
Jun Liu
Constructing Tissue-Engineered Dressing Membranes with Adipose-Derived Stem Cells and Acellular Dermal Matrix for Diabetic Wound Healing: A Comparative Study of Hypoxia- or Normoxia-Culture Modes
Stem Cells International
title Constructing Tissue-Engineered Dressing Membranes with Adipose-Derived Stem Cells and Acellular Dermal Matrix for Diabetic Wound Healing: A Comparative Study of Hypoxia- or Normoxia-Culture Modes
title_full Constructing Tissue-Engineered Dressing Membranes with Adipose-Derived Stem Cells and Acellular Dermal Matrix for Diabetic Wound Healing: A Comparative Study of Hypoxia- or Normoxia-Culture Modes
title_fullStr Constructing Tissue-Engineered Dressing Membranes with Adipose-Derived Stem Cells and Acellular Dermal Matrix for Diabetic Wound Healing: A Comparative Study of Hypoxia- or Normoxia-Culture Modes
title_full_unstemmed Constructing Tissue-Engineered Dressing Membranes with Adipose-Derived Stem Cells and Acellular Dermal Matrix for Diabetic Wound Healing: A Comparative Study of Hypoxia- or Normoxia-Culture Modes
title_short Constructing Tissue-Engineered Dressing Membranes with Adipose-Derived Stem Cells and Acellular Dermal Matrix for Diabetic Wound Healing: A Comparative Study of Hypoxia- or Normoxia-Culture Modes
title_sort constructing tissue engineered dressing membranes with adipose derived stem cells and acellular dermal matrix for diabetic wound healing a comparative study of hypoxia or normoxia culture modes
url http://dx.doi.org/10.1155/2022/2976185
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