The first abdominal aortic aneurysm organoid model replicates complex microenvironment for in vitro disease study.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-16 eCollection Date: 2025-01-01 DOI:10.7150/thno.118193
Jiaxuan Feng, Mingjie Rong, Yudong Sun, Guanglang Zhu, Guangkuo Wang, Jiping Liu, Chen Wang, Jian Zhang, Xiaochen Ma, Junyi Yan, Yaojie Wang, Youjin Li, Yu Ning, Chunhui Cai, Xinxin Han
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引用次数: 0

Abstract

Background: Abdominal Aortic Aneurysm (AAA) is a critical global health issue, affecting an estimated up to 8% of men over 65, with a complex etiology involving smoking, age and gender. However, the lack of specific drug treatments underscores the need for a robust in vitro model to advance our comprehension of AAA pathophysiology and serve as an ex vivo surrogate for drug testing. Methods: This study introduces an innovative AAA patient-derived organoid (PDO) model using a non-enzymatic procedure, a Matrigel-free system, and specialized organoid culture medium, leveraging 3-dimensional (3D) cultures to replicate the disease's microenvironment. The stability of this culture system was assessed through microscopic observation, H&E staining, immunohistochemistry (IHC), viability assays, and whole-genome sequencing (WES). Additionally, we conducted pharmacological assessments to explore the effects of drug treatments on AAA PDO. Results: Our model maintains aortic morphological integrity and pathological phenotypes, incorporates the immune microenvironment (validated by IHC markers for macrophages and lymphocytes), and adjacent tissues (loose connective tissue and vegetative blood vessels). The model demonstrates remarkable stability, confirmed by consistent genetic mutation sites throughout cultivation via WES, and cell survival after five weeks in vitro via live-cell staining. Preliminary pharmacological assessments show promising efficacy, with distinct responses to 1 μM metformin, 1 μM RU.521, or 1 μM STING-IN-2 treatments for 48 h via mass spectrometry. Conclusions: The AAA organoid model, to the best of our knowledge, is the first reported abdominal aortic aneurysm PDO model, and signifies a promising step towards therapeutic treatment options for AAA, potentially complementing existing surgical approaches.

首个腹主动脉瘤类器官模型复制复杂微环境用于体外疾病研究。
背景:腹主动脉瘤(AAA)是一个严重的全球健康问题,估计影响多达8%的65岁以上男性,其病因复杂,涉及吸烟、年龄和性别。然而,缺乏特异性药物治疗强调需要一个强大的体外模型来推进我们对AAA病理生理学的理解,并作为药物测试的离体替代品。方法:本研究引入了一种创新的AAA患者源性类器官(PDO)模型,使用非酶程序、无基质系统和专门的类器官培养基,利用三维(3D)培养来复制疾病的微环境。通过显微镜观察、H&E染色、免疫组织化学(IHC)、活力测定和全基因组测序(WES)来评估该培养系统的稳定性。此外,我们还进行了药理学评估,探讨药物治疗对AAA PDO的影响。结果:我们的模型保持了主动脉形态完整性和病理表型,结合了免疫微环境(通过巨噬细胞和淋巴细胞的免疫组化标记验证)和邻近组织(疏松结缔组织和植物血管)。该模型表现出显著的稳定性,在整个培养过程中通过WES证实了一致的基因突变位点,并在体外5周后通过活细胞染色证实了细胞存活。初步药理评估显示,通过质谱分析,1 μM二甲双胍、1 μM RU.521或1 μM STING-IN-2治疗48小时,疗效显著。结论:据我们所知,AAA类器官模型是首次报道的腹主动脉瘤PDO模型,标志着AAA治疗选择的有希望的一步,可能补充现有的手术入路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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