Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift
Abstract Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro‐inflammatory macrophage phenotype. This study investigates the therapeutic potential of int...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Bioengineering & Translational Medicine |
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| Online Access: | https://doi.org/10.1002/btm2.10711 |
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| author | Yuxin Zhang Wei Wang Liang Chen Heng Wang Dong Dong Jingjing Zhu Yu Guo Yiqun Zhou Tianyi Liu Wei Fu |
| author_facet | Yuxin Zhang Wei Wang Liang Chen Heng Wang Dong Dong Jingjing Zhu Yu Guo Yiqun Zhou Tianyi Liu Wei Fu |
| author_sort | Yuxin Zhang |
| collection | DOAJ |
| description | Abstract Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro‐inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin‐10 (IL‐10) chemically modified mRNA (modRNA)‐enriched human adipose‐derived multipotent stromal cells (hADSCs) in a well‐established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1‐methylpseudouridine‐5′‐triphosphate (m1Ψ) by substituting uridine‐5‐triphosphate. In vitro experiments demonstrated that IL‐10 modRNA‐transfected hADSCs effectively modulated macrophage polarization towards an anti‐inflammatory phenotype. In vivo experiments with a well‐established murine model demonstrated that transplantation of hADSCsmodIL‐10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re‐epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL‐10 modRNA‐enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL‐10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds. |
| format | Article |
| id | doaj-art-bb0da32f00ce457280b87bfb9f0cbb00 |
| institution | Kabale University |
| issn | 2380-6761 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj-art-bb0da32f00ce457280b87bfb9f0cbb002025-01-09T06:19:46ZengWileyBioengineering & Translational Medicine2380-67612025-01-01101n/an/a10.1002/btm2.10711Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shiftYuxin Zhang0Wei Wang1Liang Chen2Heng Wang3Dong Dong4Jingjing Zhu5Yu Guo6Yiqun Zhou7Tianyi Liu8Wei Fu9Shanghai Key Laboratory of Clinical Geriatric Medicine Huadong Hospital Shanghai ChinaShanghai Key Laboratory of Clinical Geriatric Medicine Huadong Hospital Shanghai ChinaDepartment of Plastic Surgery, Huadong Hospital, School of Medicine Fudan University Shanghai ChinaDepartment of Plastic Surgery, Huadong Hospital, School of Medicine Fudan University Shanghai ChinaDepartment of Plastic Surgery, Huadong Hospital, School of Medicine Fudan University Shanghai ChinaDepartment of Plastic Surgery, Huadong Hospital, School of Medicine Fudan University Shanghai ChinaDepartment of Plastic Surgery, Huadong Hospital, School of Medicine Fudan University Shanghai ChinaDepartment of Plastic Surgery, Huadong Hospital, School of Medicine Fudan University Shanghai ChinaShanghai Key Laboratory of Clinical Geriatric Medicine Huadong Hospital Shanghai ChinaInstitute of Pediatric Translational Medicine, Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, School of Medicine Shanghai Jiao Tong University Shanghai ChinaAbstract Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro‐inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin‐10 (IL‐10) chemically modified mRNA (modRNA)‐enriched human adipose‐derived multipotent stromal cells (hADSCs) in a well‐established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1‐methylpseudouridine‐5′‐triphosphate (m1Ψ) by substituting uridine‐5‐triphosphate. In vitro experiments demonstrated that IL‐10 modRNA‐transfected hADSCs effectively modulated macrophage polarization towards an anti‐inflammatory phenotype. In vivo experiments with a well‐established murine model demonstrated that transplantation of hADSCsmodIL‐10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re‐epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL‐10 modRNA‐enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL‐10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.https://doi.org/10.1002/btm2.10711adipose‐derived multipotent stromal cellsdiabetic woundinterleukin‐10stem cell therapytherapeutic mRNA |
| spellingShingle | Yuxin Zhang Wei Wang Liang Chen Heng Wang Dong Dong Jingjing Zhu Yu Guo Yiqun Zhou Tianyi Liu Wei Fu Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift Bioengineering & Translational Medicine adipose‐derived multipotent stromal cells diabetic wound interleukin‐10 stem cell therapy therapeutic mRNA |
| title | Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift |
| title_full | Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift |
| title_fullStr | Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift |
| title_full_unstemmed | Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift |
| title_short | Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift |
| title_sort | human adipose derived multipotent stromal cells enriched with il 10 modrna improve diabetic wound healing trigger the macrophage phenotype shift |
| topic | adipose‐derived multipotent stromal cells diabetic wound interleukin‐10 stem cell therapy therapeutic mRNA |
| url | https://doi.org/10.1002/btm2.10711 |
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