Enhanced Wound Healing and Autogenesis Through Lentiviral Transfection of Adipose-Derived Stem Cells Combined with Dermal Substitute

Background: Burns and chronic ulcers may cause severe skin loss, leading to critical health issues like shock, infection, sepsis, and multiple organ failure. Effective healing of full-thickness wounds may be challenging, with traditional methods facing limitations due to tissue shortage, infection,...

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Main Authors: Shiqi Wang, Dinghui Gao, Mingyu Li, Qian Wang, Xuanyu Du, Siming Yuan
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/12/2844
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author Shiqi Wang
Dinghui Gao
Mingyu Li
Qian Wang
Xuanyu Du
Siming Yuan
author_facet Shiqi Wang
Dinghui Gao
Mingyu Li
Qian Wang
Xuanyu Du
Siming Yuan
author_sort Shiqi Wang
collection DOAJ
description Background: Burns and chronic ulcers may cause severe skin loss, leading to critical health issues like shock, infection, sepsis, and multiple organ failure. Effective healing of full-thickness wounds may be challenging, with traditional methods facing limitations due to tissue shortage, infection, and lack of structural support. Methods: This study explored the combined use of gene transfection and dermal substitutes to improve wound healing. We used the DGTM (genes: <i>DNP63A</i>, <i>GRHL2</i>, <i>TFAP2A</i>, and <i>MYC</i>) factors to transfect adipose-derived stem cells (ADSCs), inducing their differentiation into keratinocytes. These transfected ADSCs were then incorporated into Pelnac<sup>®</sup> dermal substitutes to enhance vascularization and cellular proliferation for better healing outcomes. Results: Gene transfer using DGTM factors successfully induced keratinocyte differentiation in ADSCs. The application of these differentiated cells with Pelnac<sup>®</sup> dermal substitute to dermal wounds in mice resulted in the formation of skin tissue with a normal epidermal layer and proper collagen organization. This method alleviates the tediousness of the multiple transfection steps in previous protocols and the safety issues caused by using viral transfection reagents directly on the wound. Additionally, the inclusion of dermal substitutes addressed the lack of collagen and elastic fibers, promoting the formation of tissue resembling healthy skin rather than scar tissue. Conclusion: Integrating DGTM factor-transfected ADSCs with dermal substitutes represents a novel strategy for enhancing the healing of full-thickness wounds. Further research and clinical trials are warranted to optimize and validate this innovative approach for broader clinical applications.
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spelling doaj-art-15b2f24c852d4af8b4e5ed01a13fc27e2024-12-27T14:13:02ZengMDPI AGBiomedicines2227-90592024-12-011212284410.3390/biomedicines12122844Enhanced Wound Healing and Autogenesis Through Lentiviral Transfection of Adipose-Derived Stem Cells Combined with Dermal SubstituteShiqi Wang0Dinghui Gao1Mingyu Li2Qian Wang3Xuanyu Du4Siming Yuan5Department of Plastic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, ChinaDepartment of Plastic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, ChinaDepartment of Plastic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, ChinaDepartment of Plastic Surgery, Jinling Hospital, Nanjing School of Clinical Medicine, Southern Medical University, Nanjing 210002, ChinaDepartment of Plastic Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing 210002, ChinaDepartment of Plastic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, ChinaBackground: Burns and chronic ulcers may cause severe skin loss, leading to critical health issues like shock, infection, sepsis, and multiple organ failure. Effective healing of full-thickness wounds may be challenging, with traditional methods facing limitations due to tissue shortage, infection, and lack of structural support. Methods: This study explored the combined use of gene transfection and dermal substitutes to improve wound healing. We used the DGTM (genes: <i>DNP63A</i>, <i>GRHL2</i>, <i>TFAP2A</i>, and <i>MYC</i>) factors to transfect adipose-derived stem cells (ADSCs), inducing their differentiation into keratinocytes. These transfected ADSCs were then incorporated into Pelnac<sup>®</sup> dermal substitutes to enhance vascularization and cellular proliferation for better healing outcomes. Results: Gene transfer using DGTM factors successfully induced keratinocyte differentiation in ADSCs. The application of these differentiated cells with Pelnac<sup>®</sup> dermal substitute to dermal wounds in mice resulted in the formation of skin tissue with a normal epidermal layer and proper collagen organization. This method alleviates the tediousness of the multiple transfection steps in previous protocols and the safety issues caused by using viral transfection reagents directly on the wound. Additionally, the inclusion of dermal substitutes addressed the lack of collagen and elastic fibers, promoting the formation of tissue resembling healthy skin rather than scar tissue. Conclusion: Integrating DGTM factor-transfected ADSCs with dermal substitutes represents a novel strategy for enhancing the healing of full-thickness wounds. Further research and clinical trials are warranted to optimize and validate this innovative approach for broader clinical applications.https://www.mdpi.com/2227-9059/12/12/2844adipose-derived stem cells (ADSCs)gene transfectionkeratinocyte differentiationdermal substituteswound healing
spellingShingle Shiqi Wang
Dinghui Gao
Mingyu Li
Qian Wang
Xuanyu Du
Siming Yuan
Enhanced Wound Healing and Autogenesis Through Lentiviral Transfection of Adipose-Derived Stem Cells Combined with Dermal Substitute
Biomedicines
adipose-derived stem cells (ADSCs)
gene transfection
keratinocyte differentiation
dermal substitutes
wound healing
title Enhanced Wound Healing and Autogenesis Through Lentiviral Transfection of Adipose-Derived Stem Cells Combined with Dermal Substitute
title_full Enhanced Wound Healing and Autogenesis Through Lentiviral Transfection of Adipose-Derived Stem Cells Combined with Dermal Substitute
title_fullStr Enhanced Wound Healing and Autogenesis Through Lentiviral Transfection of Adipose-Derived Stem Cells Combined with Dermal Substitute
title_full_unstemmed Enhanced Wound Healing and Autogenesis Through Lentiviral Transfection of Adipose-Derived Stem Cells Combined with Dermal Substitute
title_short Enhanced Wound Healing and Autogenesis Through Lentiviral Transfection of Adipose-Derived Stem Cells Combined with Dermal Substitute
title_sort enhanced wound healing and autogenesis through lentiviral transfection of adipose derived stem cells combined with dermal substitute
topic adipose-derived stem cells (ADSCs)
gene transfection
keratinocyte differentiation
dermal substitutes
wound healing
url https://www.mdpi.com/2227-9059/12/12/2844
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