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无细胞脂肪提取物通过胶原蛋白重塑和抗血管生成抑制增生性瘢痕形成。

Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis.

作者信息

Sun Junchao, Zhao Yujie, Qu Zhoujiang, Sun Shudong, Wang Kun

机构信息

School of Clinical Medicine, Shandong Second Medical University, Weifang, China.

Department of Burns and Wound Repair, Weifang People's Hospital, Shandong Second Medical University, Weifang, China.

出版信息

Open Med (Wars). 2025 Aug 22;20(1):20251249. doi: 10.1515/med-2025-1249. eCollection 2025.

DOI:10.1515/med-2025-1249
PMID:40918159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12413796/
Abstract

OBJECTIVE

Hypertrophic scars (HS) are a fibrotic proliferative disorder that results from an abnormal wound healing process, presenting significant challenges for clinical intervention. The primary characteristics of HS include excessive collagen deposition and angiogenesis. In recent years, the study of mesenchymal stem cells (MSCs) and their derived exosomes has emerged as a prominent area of research within the academic community. However, the therapeutic application of MSCs is impeded by several challenges, including immune rejection, sourcing limitations, ethical dilemmas, and difficulties related to the scalability of exosome production. Cell-free adipose extract (CEFAE), a novel bioproduct derived from adipose tissue, is rich in various active protein factors that are essential for MSCs and their exosomes. CEFAE presents several advantages, including low immunogenicity, non-tumorigenicity, and a high degree of clinical safety. However, the application of CEFAE in the prevention and treatment of scar formation has not been adequately validated through experimental studies.

METHODS

This research established a rabbit ear scar model, establishing a control group, a low-concentration CEFAE group (L-CEFAE), and a high-concentration CEFAE group (H-CEFAE) to evaluate wound treatment. Observations of scar changes were conducted at 14 and 28 days post-treatment, supplemented by histological and immunohistochemical analyses.

RESULTS

Histological analysis revealed that the H-CEFAE group achieved optimal outcomes, with the lowest collagen deposition, thinnest epidermal/dermal thickness, and the most orderly collagen alignment. Furthermore, the formation of new blood vessels in the H-CEFAE group showed a significant reduction over time, resulting in decreased blood supply, which is beneficial for suppressing scar tissue development. Quantification of COL I, COL III, and vascular endothelial growth factor also supports these results.

CONCLUSION

The findings indicated that high-concentration CEFAE has a beneficial preventive and therapeutic effect on scar proliferation. Furthermore, the study explored the potential mechanisms by which CEFAE inhibits scar proliferation, thereby providing novel therapeutic strategies for the prevention and management of clinical scars.

摘要

目的

肥厚性瘢痕(HS)是一种由异常伤口愈合过程导致的纤维化增殖性疾病,给临床干预带来了重大挑战。HS的主要特征包括胶原蛋白过度沉积和血管生成。近年来,间充质干细胞(MSCs)及其衍生外泌体的研究已成为学术界一个突出的研究领域。然而,MSCs的治疗应用受到多种挑战的阻碍,包括免疫排斥、来源限制、伦理困境以及与外泌体生产可扩展性相关的困难。无细胞脂肪提取物(CEFAE)是一种源自脂肪组织的新型生物制品,富含对MSCs及其外泌体至关重要的各种活性蛋白因子。CEFAE具有多种优势,包括低免疫原性、无致瘤性和高度的临床安全性。然而,CEFAE在预防和治疗瘢痕形成中的应用尚未通过实验研究得到充分验证。

方法

本研究建立了兔耳瘢痕模型,设立对照组、低浓度CEFAE组(L - CEFAE)和高浓度CEFAE组(H - CEFAE)以评估伤口治疗效果。在治疗后14天和28天对瘢痕变化进行观察,并辅以组织学和免疫组织化学分析。

结果

组织学分析显示,H - CEFAE组取得了最佳效果,胶原蛋白沉积最少,表皮/真皮厚度最薄,胶原蛋白排列最有序。此外,H - CEFAE组新血管的形成随时间显著减少,导致血液供应减少,这有利于抑制瘢痕组织的发展。对I型胶原蛋白、III型胶原蛋白和血管内皮生长因子的定量分析也支持这些结果。

结论

研究结果表明,高浓度CEFAE对瘢痕增殖具有有益的预防和治疗作用。此外,该研究探索了CEFAE抑制瘢痕增殖的潜在机制,从而为临床瘢痕的预防和管理提供了新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/5ffca34d7ca7/j_med-2025-1249-fig006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/252bd235fbff/j_med-2025-1249-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/8179bdfd43c7/j_med-2025-1249-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/9d9bbd0f1836/j_med-2025-1249-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/97fc28c83c23/j_med-2025-1249-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/103b510be64d/j_med-2025-1249-fig005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/5ffca34d7ca7/j_med-2025-1249-fig006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/252bd235fbff/j_med-2025-1249-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/8179bdfd43c7/j_med-2025-1249-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/9d9bbd0f1836/j_med-2025-1249-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/97fc28c83c23/j_med-2025-1249-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/103b510be64d/j_med-2025-1249-fig005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4bc/12413796/5ffca34d7ca7/j_med-2025-1249-fig006.jpg

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