正常和肺癌相关成纤维细胞在微血管网络形成中的不同作用

IF 6.6 3区 医学 Q1 ENGINEERING, BIOMEDICAL
APL Bioengineering Pub Date : 2024-03-19 eCollection Date: 2024-03-01 DOI:10.1063/5.0188238
Naveen R Natesh, Pankaj Mogha, Alan Chen, Scott J Antonia, Shyni Varghese
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引用次数: 0

摘要

可灌注的微血管网络为研究正常和受损的血管组织以及癌细胞转移等现象提供了前景广阔的三维体外模型。这些微血管网络的工程设计通常涉及使用由成纤维细胞稳定的内皮细胞来生成强健稳定的血管。然而,成纤维细胞具有高度异质性,可能对微血管结构产生不同的影响。在这里,我们研究了正常和癌症相关肺成纤维细胞对可灌注微血管网络的形成和功能的影响。我们研究了癌症相关成纤维细胞在与内皮细胞直接(并源)和间接(旁源)接触培养时对微血管网络的影响,发现并源共培养会抑制微血管的生成,而旁源共培养则会抑制微血管的功能。此外,我们还探究了癌症相关成纤维细胞与正常人肺成纤维细胞之间的分泌因子差异,确定了几种可能影响微血管形态和功能的细胞因子。这些研究结果表明,癌症相关成纤维细胞在与肿瘤相关的异常微血管中的潜在作用,以及这种体外平台在确定新的治疗靶点和/或可防止异常血管结构形成的药物方面的合理应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Differential roles of normal and lung cancer-associated fibroblasts in microvascular network formation.

Perfusable microvascular networks offer promising three-dimensional in vitro models to study normal and compromised vascular tissues as well as phenomena such as cancer cell metastasis. Engineering of these microvascular networks generally involves the use of endothelial cells stabilized by fibroblasts to generate robust and stable vasculature. However, fibroblasts are highly heterogenous and may contribute variably to the microvascular structure. Here, we study the effect of normal and cancer-associated lung fibroblasts on the formation and function of perfusable microvascular networks. We examine the influence of cancer-associated fibroblasts on microvascular networks when cultured in direct (juxtacrine) and indirect (paracrine) contacts with endothelial cells, discovering a generative inhibition of microvasculature in juxtacrine co-cultures and a functional inhibition in paracrine co-cultures. Furthermore, we probed the secreted factors differential between cancer-associated fibroblasts and normal human lung fibroblasts, identifying several cytokines putatively influencing the resulting microvasculature morphology and functionality. These findings suggest the potential contribution of cancer-associated fibroblasts in aberrant microvasculature associated with tumors and the plausible application of such in vitro platforms in identifying new therapeutic targets and/or agents that can prevent formation of aberrant vascular structures.

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来源期刊
APL Bioengineering
APL Bioengineering ENGINEERING, BIOMEDICAL-
CiteScore
9.30
自引率
6.70%
发文量
39
审稿时长
19 weeks
期刊介绍: APL Bioengineering is devoted to research at the intersection of biology, physics, and engineering. The journal publishes high-impact manuscripts specific to the understanding and advancement of physics and engineering of biological systems. APL Bioengineering is the new home for the bioengineering and biomedical research communities. APL Bioengineering publishes original research articles, reviews, and perspectives. Topical coverage includes: -Biofabrication and Bioprinting -Biomedical Materials, Sensors, and Imaging -Engineered Living Systems -Cell and Tissue Engineering -Regenerative Medicine -Molecular, Cell, and Tissue Biomechanics -Systems Biology and Computational Biology
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