Human growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repair
Objective: Human growth hormone (HGH) enhances wound healing by promoting cell proliferation, angiogenesis, and tissue regeneration. This study investigated the effects of HGH-overexpressing Adipose-derived stem cells (HGH-ADSCs) on fibroblast function, ERK pathway activation, and burn wound healing...
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Elsevier
2025-12-01
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| Series: | Regenerative Therapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320425001567 |
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| author | Yang Shao Mei Han Guodong Song Cong Gao |
| author_facet | Yang Shao Mei Han Guodong Song Cong Gao |
| author_sort | Yang Shao |
| collection | DOAJ |
| description | Objective: Human growth hormone (HGH) enhances wound healing by promoting cell proliferation, angiogenesis, and tissue regeneration. This study investigated the effects of HGH-overexpressing Adipose-derived stem cells (HGH-ADSCs) on fibroblast function, ERK pathway activation, and burn wound healing. Methods: ADSCs were isolated from adipose tissue, characterized via CD marker expression, and confirmed for multipotency using Oil Red O (adipogenesis), Alizarin Red S (osteogenesis), and Alcian Blue staining (chondrogenesis). ADSCs were then transduced with a lentiviral vector carrying HGH, generating HGH-ADSCs and confirmed by qRT-PCR. Fibroblasts (HDF-a) were co-cultured were co-cultured under HGH-ADSCs-conditioned medium and ADSCs-conditioned medium to assess proliferation (MTT assay), migration and invasion (Transwell), apoptosis (flow cytometry), and G0/G1 cell cycle progression. Western blotting determined ERK activation, and SCH772984 (ERK inhibitor) was used to confirm pathway dependency. A burn rat model was established with three treatment groups: HGH-ADSCs, ADSCs, and saline. and histopathology (H&E, TUNEL staining) analyzed epithelial regeneration and apoptosis. ELISA and biochemical assays quantified TNF-α, IL-1β, IL-6, MDA, SOD, and CAT in wound tissue homogenates. Results: HGH-ADSCs significantly enhanced fibroblast proliferation, migration, invasion, and prolonged G0/G1 phase while reducing apoptosis (P < 0.05). ERK inhibition abolished these effects (P < 0.05). In vivo, HGH-ADSCs accelerated wound closure (P < 0.05), enhanced epithelialization, reduced inflammation, and increased collagen formation. Inflammatory cytokines (TNF-α, IL-1β, IL-6) and MDA were lowest, while SOD and CAT were highest in HGH-ADSC-treated wounds (P < 0.05). Conclusion: ADSCs overexpressing HGH promote fibroblast activity, activate ERK signaling, and accelerate burn wound healing, demonstrating strong therapeutic potential. |
| format | Article |
| id | doaj-art-c1c92f1bca1e45efbbb4be63c1c12de4 |
| institution | Matheson Library |
| issn | 2352-3204 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
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| series | Regenerative Therapy |
| spelling | doaj-art-c1c92f1bca1e45efbbb4be63c1c12de42025-07-31T04:53:34ZengElsevierRegenerative Therapy2352-32042025-12-0130465475Human growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repairYang Shao0Mei Han1Guodong Song2Cong Gao3Department of Burns and Plastic Surgery & Department of Wound Repair, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250013, China; Department of Burns and Plastic Surgery & Department of Wound Repair, Jinan Central Hospital, Jinan, Shandong, 250013, ChinaDepartment of Burns and Plastic Surgery & Department of Wound Repair, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250013, China; Department of Burns and Plastic Surgery & Department of Wound Repair, Jinan Central Hospital, Jinan, Shandong, 250013, ChinaDepartment of Burns and Plastic Surgery & Department of Wound Repair, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250013, China; Department of Burns and Plastic Surgery & Department of Wound Repair, Jinan Central Hospital, Jinan, Shandong, 250013, ChinaDepartment of Burns and Plastic Surgery & Department of Wound Repair, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250013, China; Department of Burns and Plastic Surgery & Department of Wound Repair, Jinan Central Hospital, Jinan, Shandong, 250013, China; Corresponding author. Department of Burns and Plastic Surgery & Department of Wound Repair, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250013, China.Objective: Human growth hormone (HGH) enhances wound healing by promoting cell proliferation, angiogenesis, and tissue regeneration. This study investigated the effects of HGH-overexpressing Adipose-derived stem cells (HGH-ADSCs) on fibroblast function, ERK pathway activation, and burn wound healing. Methods: ADSCs were isolated from adipose tissue, characterized via CD marker expression, and confirmed for multipotency using Oil Red O (adipogenesis), Alizarin Red S (osteogenesis), and Alcian Blue staining (chondrogenesis). ADSCs were then transduced with a lentiviral vector carrying HGH, generating HGH-ADSCs and confirmed by qRT-PCR. Fibroblasts (HDF-a) were co-cultured were co-cultured under HGH-ADSCs-conditioned medium and ADSCs-conditioned medium to assess proliferation (MTT assay), migration and invasion (Transwell), apoptosis (flow cytometry), and G0/G1 cell cycle progression. Western blotting determined ERK activation, and SCH772984 (ERK inhibitor) was used to confirm pathway dependency. A burn rat model was established with three treatment groups: HGH-ADSCs, ADSCs, and saline. and histopathology (H&E, TUNEL staining) analyzed epithelial regeneration and apoptosis. ELISA and biochemical assays quantified TNF-α, IL-1β, IL-6, MDA, SOD, and CAT in wound tissue homogenates. Results: HGH-ADSCs significantly enhanced fibroblast proliferation, migration, invasion, and prolonged G0/G1 phase while reducing apoptosis (P < 0.05). ERK inhibition abolished these effects (P < 0.05). In vivo, HGH-ADSCs accelerated wound closure (P < 0.05), enhanced epithelialization, reduced inflammation, and increased collagen formation. Inflammatory cytokines (TNF-α, IL-1β, IL-6) and MDA were lowest, while SOD and CAT were highest in HGH-ADSC-treated wounds (P < 0.05). Conclusion: ADSCs overexpressing HGH promote fibroblast activity, activate ERK signaling, and accelerate burn wound healing, demonstrating strong therapeutic potential.http://www.sciencedirect.com/science/article/pii/S2352320425001567BurnsWound repairGrowth hormoneERK pathwayAdipose-derived mesenchymal stem cells |
| spellingShingle | Yang Shao Mei Han Guodong Song Cong Gao Human growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repair Regenerative Therapy Burns Wound repair Growth hormone ERK pathway Adipose-derived mesenchymal stem cells |
| title | Human growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repair |
| title_full | Human growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repair |
| title_fullStr | Human growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repair |
| title_full_unstemmed | Human growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repair |
| title_short | Human growth hormone-overexpressing adipose-derived stem cells enhance fibroblast activity and accelerate burn wound healing via ERK pathway therapeutic potential of ADSCs in burn wound repair |
| title_sort | human growth hormone overexpressing adipose derived stem cells enhance fibroblast activity and accelerate burn wound healing via erk pathway therapeutic potential of adscs in burn wound repair |
| topic | Burns Wound repair Growth hormone ERK pathway Adipose-derived mesenchymal stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S2352320425001567 |
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