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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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-12-01
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| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320425001567 |
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| Summary: | 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. |
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| ISSN: | 2352-3204 |