从小鼠乳腺癌细胞中提取的外泌体促进糖尿病伤口愈合

IF 4.4 4区 医学 Q2 CELL & TISSUE ENGINEERING Tissue engineering and regenerative medicine Pub Date : 2024-06-01 Epub Date: 2024-03-12 DOI:10.1007/s13770-024-00629-1
Chao Zhang, Wenchi Xiao, Hao Wang, Linxiao Li, Yan Yang, Yongwei Hao, Zhihao Xu, Hongli Chen, Wenbin Nan
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引用次数: 0

摘要

背景:据报道,源自乳腺癌的外泌体具有促进细胞增殖、迁移和血管生成的作用,这有可能加速糖尿病伤口的愈合过程。本研究旨在探讨源自 4T1 小鼠乳腺癌细胞(TEXs)的外泌体在糖尿病伤口愈合过程中的功能:方法:利用CCK-8和伤口愈合试验评估原代小鼠皮肤成纤维细胞的增殖和迁移,同时利用管形成试验评估HUVECs的管形成。利用高通量测序、RT-qPCR 和细胞实验检测了 miR-126a-3p 在 HUVECs 体外功能中的作用。体内研究采用了糖尿病患者的全厚切除伤口模型,以探索 TEXs 的潜在治疗功效。研究利用免疫组化和免疫荧光技术评估皮肤组织的组织学变化:结果:研究结果表明,TEXs 可通过激活细胞迁移、增殖和血管生成促进糖尿病伤口愈合。在TEXs中观察到了miR-126a-3p的上调,并证明它能从4T1细胞有效转移到HUVEC细胞。PI3K/Akt通路的激活归因于来自TEXs的miR-126a-3p:结论:TEXs 可通过激活细胞迁移、增殖和血管生成促进慢性伤口愈合。研究发现,源自TEXs的miR-126a-3p可激活PI3K/Akt通路,这为增强用TEXs处理的伤口的再生能力提供了潜在途径。
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Exosomes Derived from Mouse Breast Carcinoma Cells Facilitate Diabetic Wound Healing.

Background: Exosomes derived from breast cancer have been reported to play a role in promoting cell proliferation, migration, and angiogenesis, which has the potential to accelerate the healing process of diabetic wounds. The aim of this investigation was to examine the function of exosomes originating from 4T1 mouse breast carcinoma cells (TEXs) in the process of diabetic wound healing.

Methods: The assessment of primary mouse skin fibroblasts cell proliferation and migration was conducted through the utilization of CCK-8 and wound healing assays, while the tube formation of HUVECs was evaluated by tube formation assay. High-throughput sequencing, RT-qPCR and cell experiments were used to detect the roles of miR-126a-3p in HUVECs functions in vitro. The in vivo study employed a model of full-thickness excisional wounds in diabetic subjects to explore the potential therapeutic benefits of TEXs. Immunohistochemical and immunofluorescent techniques were utilized to evaluate histological changes in skin tissues.

Results: The findings suggested that TEXs facilitate diabetic wound healing through the activation of cell migration, proliferation, and angiogenesis. An upregulation of miR-126a-3p has been observed in TEXs, and it has demonstrated efficient transferability from 4T1 cells to HUVEC cells. The activation of the PI3K/Akt pathway has been attributed to miR-126a-3p derived from TEXs.

Conclusions: The promotion of chronic wound healing can be facilitated by TEXs through the activation of cellular migration, proliferation, and angiogenesis. The activation of the PI3K/Akt pathway by miR-126a-3p originating from TEXs has been discovered, indicating a potential avenue for enhancing the regenerative capabilities of wounds treated with TEXs.

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来源期刊
Tissue engineering and regenerative medicine
Tissue engineering and regenerative medicine CELL & TISSUE ENGINEERING-ENGINEERING, BIOMEDICAL
CiteScore
6.80
自引率
5.60%
发文量
83
审稿时长
6-12 weeks
期刊介绍: Tissue Engineering and Regenerative Medicine (Tissue Eng Regen Med, TERM), the official journal of the Korean Tissue Engineering and Regenerative Medicine Society, is a publication dedicated to providing research- based solutions to issues related to human diseases. This journal publishes articles that report substantial information and original findings on tissue engineering, medical biomaterials, cells therapy, stem cell biology and regenerative medicine.
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