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

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy Pub Date : 2025-07-30 DOI:10.1016/j.reth.2025.07.002

Yang Shao , Mei Han , Guodong Song , Cong Gao

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引用次数: 0

Abstract

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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过度表达人类生长激素的脂肪源性干细胞通过ERK通路增强成纤维细胞活性并加速烧伤创面愈合

目的：人生长激素（HGH）通过促进细胞增殖、血管生成和组织再生来促进伤口愈合。本研究探讨了过表达hgh的脂肪源性干细胞（HGH-ADSCs）对成纤维细胞功能、ERK通路激活和烧伤创面愈合的影响。方法从脂肪组织中分离sadscs，通过CD标记表达进行鉴定，并通过油红O（脂肪形成）、茜素红S（成骨）和阿利新蓝染色（软骨形成）证实其多能性。然后用携带HGH的慢病毒载体转导ADSCs，生成HGH-ADSCs，并通过qRT-PCR证实。成纤维细胞（HDF-a）在hgh - adscs条件培养基和adscs条件培养基中共培养，以评估增殖（MTT试验）、迁移和侵袭（Transwell）、凋亡（流式细胞术）和G0/G1细胞周期进展。Western blotting检测ERK活化，SCH772984 （ERK抑制剂）检测通路依赖性。采用HGH-ADSCs、ADSCs、生理盐水三组治疗大鼠烧伤模型。组织病理学（H&；E， TUNEL染色）分析上皮再生和凋亡。ELISA和生化分析定量了伤口组织匀浆中的TNF-α、IL-1β、IL-6、MDA、SOD和CAT。结果shgh - adscs显著增强成纤维细胞增殖、迁移、侵袭，延长G0/G1期，减少细胞凋亡(P <；0.05)。ERK抑制消除了这些影响(P <；0.05)。在体内，HGH-ADSCs加速伤口愈合(P <；0.05)，上皮化增强，炎症减少，胶原形成增加。炎症因子（TNF-α, IL-1β, IL-6）和MDA在hgh - adsc处理的伤口中最低，SOD和CAT在hgh - adsc处理的伤口中最高(P <；0.05)。结论过表达HGH的adscs促进成纤维细胞活性，激活ERK信号，促进烧伤创面愈合，具有较强的治疗潜力。

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来源期刊

Regenerative Therapy Engineering-Biomedical Engineering

CiteScore

6.00

自引率

2.30%

发文量

106

审稿时长

49 days

期刊介绍： Regenerative Therapy is the official peer-reviewed online journal of the Japanese Society for Regenerative Medicine. Regenerative Therapy is a multidisciplinary journal that publishes original articles and reviews of basic research, clinical translation, industrial development, and regulatory issues focusing on stem cell biology, tissue engineering, and regenerative medicine.