The Effect of Conditioned Medium from Angiopoietin-1 Gene-Modified Mesenchymal Stem Cells on Wound Healing in a Diabetic Mouse Model

Introduction: Mesenchymal stem cells (MSCs) have been introduced as a promising treatment for diabetic wounds. The effects of stem cell therapy are thought to be caused by bioactive molecules secreted by stem cells. Stem cell-based gene therapies can target bioactive molecules. Therefore, treatment...

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Main Authors: Qiong Deng, Shenzhen Pan, Fangzhou Du, Hongfei Sang, Zhixin Cai, Xiaoyu Xu, Qian Wei, Shuang Yu, Jingzhong Zhang, Chenglong Li
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Bioengineering
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Online Access:https://www.mdpi.com/2306-5354/11/12/1244
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author Qiong Deng
Shenzhen Pan
Fangzhou Du
Hongfei Sang
Zhixin Cai
Xiaoyu Xu
Qian Wei
Shuang Yu
Jingzhong Zhang
Chenglong Li
author_facet Qiong Deng
Shenzhen Pan
Fangzhou Du
Hongfei Sang
Zhixin Cai
Xiaoyu Xu
Qian Wei
Shuang Yu
Jingzhong Zhang
Chenglong Li
author_sort Qiong Deng
collection DOAJ
description Introduction: Mesenchymal stem cells (MSCs) have been introduced as a promising treatment for diabetic wounds. The effects of stem cell therapy are thought to be caused by bioactive molecules secreted by stem cells. Stem cell-based gene therapies can target bioactive molecules. Therefore, treatment using conditioned medium (CM) derived from genetically engineered stem cells has been proposed as an alternative option for diabetic ulcer care. Methods: MSCs derived from human umbilical cords were obtained and engineered to overexpress the angiogenin-1 gene (MSCs<sup>Ang1</sup>) through plasmid transfection. This study extracted conditioned medium from MSCs (MSC-CM) or MSCs<sup>Ang1</sup>(MSC<sup>Ang1</sup>-CM) for wound treatment applications. Via in vitro experiments, the proangiogenic effects of MSC<sup>Ang1</sup>-CM were assessed via the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Furthermore, the efficacy of MSC<sup>Ang1</sup>-CM in promoting wound healing, re-epithelialization, hair follicle, and angiogenesis was evaluated via a diabetic mouse skin defect model. Results: In vitro assays demonstrated that MSC<sup>Ang1</sup>-CM significantly enhanced HUVECs’ functions, including migration and tube formation. In vivo assays revealed that MSC<sup>Ang1</sup>-CM exhibited notable advancements in healing speed, re-epithelialization, hair follicle, and angiogenesis. Conclusion: These results indicate that MSC<sup>Ang1</sup>-CM can promote wound healing in diabetic mice and make the vascular structure in regenerated tissues more stable without inducing tissue fibrosis, providing a new therapeutic strategy for treating diabetic skin wounds. This provides a valuable theoretical basis for further research on regenerative medicine and cell therapy.
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spelling doaj-art-cb0681010f2d4d2499525f3d5041d4b52024-12-27T14:11:36ZengMDPI AGBioengineering2306-53542024-12-011112124410.3390/bioengineering11121244The Effect of Conditioned Medium from Angiopoietin-1 Gene-Modified Mesenchymal Stem Cells on Wound Healing in a Diabetic Mouse ModelQiong Deng0Shenzhen Pan1Fangzhou Du2Hongfei Sang3Zhixin Cai4Xiaoyu Xu5Qian Wei6Shuang Yu7Jingzhong Zhang8Chenglong Li9Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaDepartment of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaSchool of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaDepartment of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaDepartment of Radiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441000, ChinaSchool of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaSchool of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaSchool of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, ChinaDepartment of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215000, ChinaIntroduction: Mesenchymal stem cells (MSCs) have been introduced as a promising treatment for diabetic wounds. The effects of stem cell therapy are thought to be caused by bioactive molecules secreted by stem cells. Stem cell-based gene therapies can target bioactive molecules. Therefore, treatment using conditioned medium (CM) derived from genetically engineered stem cells has been proposed as an alternative option for diabetic ulcer care. Methods: MSCs derived from human umbilical cords were obtained and engineered to overexpress the angiogenin-1 gene (MSCs<sup>Ang1</sup>) through plasmid transfection. This study extracted conditioned medium from MSCs (MSC-CM) or MSCs<sup>Ang1</sup>(MSC<sup>Ang1</sup>-CM) for wound treatment applications. Via in vitro experiments, the proangiogenic effects of MSC<sup>Ang1</sup>-CM were assessed via the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Furthermore, the efficacy of MSC<sup>Ang1</sup>-CM in promoting wound healing, re-epithelialization, hair follicle, and angiogenesis was evaluated via a diabetic mouse skin defect model. Results: In vitro assays demonstrated that MSC<sup>Ang1</sup>-CM significantly enhanced HUVECs’ functions, including migration and tube formation. In vivo assays revealed that MSC<sup>Ang1</sup>-CM exhibited notable advancements in healing speed, re-epithelialization, hair follicle, and angiogenesis. Conclusion: These results indicate that MSC<sup>Ang1</sup>-CM can promote wound healing in diabetic mice and make the vascular structure in regenerated tissues more stable without inducing tissue fibrosis, providing a new therapeutic strategy for treating diabetic skin wounds. This provides a valuable theoretical basis for further research on regenerative medicine and cell therapy.https://www.mdpi.com/2306-5354/11/12/1244mesenchymal stem cellconditioned mediumAngiopoietin 1diabetic wound healingangiogenesis
spellingShingle Qiong Deng
Shenzhen Pan
Fangzhou Du
Hongfei Sang
Zhixin Cai
Xiaoyu Xu
Qian Wei
Shuang Yu
Jingzhong Zhang
Chenglong Li
The Effect of Conditioned Medium from Angiopoietin-1 Gene-Modified Mesenchymal Stem Cells on Wound Healing in a Diabetic Mouse Model
Bioengineering
mesenchymal stem cell
conditioned medium
Angiopoietin 1
diabetic wound healing
angiogenesis
title The Effect of Conditioned Medium from Angiopoietin-1 Gene-Modified Mesenchymal Stem Cells on Wound Healing in a Diabetic Mouse Model
title_full The Effect of Conditioned Medium from Angiopoietin-1 Gene-Modified Mesenchymal Stem Cells on Wound Healing in a Diabetic Mouse Model
title_fullStr The Effect of Conditioned Medium from Angiopoietin-1 Gene-Modified Mesenchymal Stem Cells on Wound Healing in a Diabetic Mouse Model
title_full_unstemmed The Effect of Conditioned Medium from Angiopoietin-1 Gene-Modified Mesenchymal Stem Cells on Wound Healing in a Diabetic Mouse Model
title_short The Effect of Conditioned Medium from Angiopoietin-1 Gene-Modified Mesenchymal Stem Cells on Wound Healing in a Diabetic Mouse Model
title_sort effect of conditioned medium from angiopoietin 1 gene modified mesenchymal stem cells on wound healing in a diabetic mouse model
topic mesenchymal stem cell
conditioned medium
Angiopoietin 1
diabetic wound healing
angiogenesis
url https://www.mdpi.com/2306-5354/11/12/1244
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