Obesity-Associated Conditions Hinder Solute Drainage Function of Engineered Human Lymphatic Vessels.

IF 2.3 4区医学 Q3 BIOPHYSICS

Cellular and molecular bioengineering Pub Date : 2025-01-23 eCollection Date: 2025-02-01 DOI:10.1007/s12195-024-00840-z

Alex J Seibel, Cheyanne L Frosti, Abderrahman R Tlemçani, Nikhil Lahiri, Joely A Brammer-DePuy, Matthew D Layne, Joe Tien

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引用次数: 0

Abstract

Purpose: Obesity is associated with poor lymphatic solute drainage. It is unclear whether the chronic inflammation, hypoxia, and hyperlipidemia that are together associated with obesity cause impaired drainage function, and if so, whether these conditions act directly on lymphatic endothelial cells (LECs) or are indirectly mediated by the mechanical properties or cellular composition of the surrounding tissue.

Methods: We engineered blind-ended lymphatic vessels in type I collagen gels and simulated the obese microenvironment with a cocktail of tumor necrosis factor (TNF)-α, cobalt chloride (CoCl₂), and oleate, which model inflammation, hypoxia, and hyperlipidemia, respectively. We compared the solute drainage rate and leakage of lymphatics that were exposed to simulated obesity or not. We performed similar assays with lymphatics in stiffened gels, in adipocyte-laden gels, or in the presence of conditioned medium (CM) from adipose cells treated with the same cocktail.

Results: Lymphatics that were exposed to simulated obesity exhibited more gaps in endothelial junctions, leaked more solute, and drained solute less quickly than control lymphatics did, regardless of matrix stiffness. CM from adipose cells that were exposed to simulated obesity did not affect lymphatics. Lymphatics in adipocyte-laden gels did not exhibit worse drainage function when exposed to simulated obesity.

Conclusions: The combination of obesity-associated inflammation, hypoxia, and hyperlipidemia impairs lymphatic solute drainage and does so by acting directly on LECs. Surprisingly, adipocytes may play a protective role in preventing obesity-associated conditions from impairing lymphatic solute drainage.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-024-00840-z.

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肥胖相关疾病阻碍工程人类淋巴管的溶质排水功能。

目的：肥胖与淋巴溶质排泄不良有关。慢性炎症、缺氧和高脂血症是否与肥胖相关导致引流功能受损尚不清楚，如果是这样，这些情况是直接作用于淋巴内皮细胞（LECs），还是由周围组织的机械特性或细胞组成间接介导。方法：我们在I型胶原凝胶中设计盲端淋巴管，并用肿瘤坏死因子(TNF)-α、氯化钴（CoCl2）和油酸盐的混合物模拟肥胖微环境，分别模拟炎症、缺氧和高脂血症。我们比较了模拟肥胖组和非模拟肥胖组的溶质引流率和淋巴渗漏率。我们在硬化凝胶、脂肪细胞负载凝胶或用相同混合物处理的脂肪细胞的条件培养基（CM）中对淋巴管进行了类似的测定。结果：无论基质硬度如何，暴露于模拟肥胖的淋巴管在内皮连接处表现出更多的间隙，泄漏更多的溶质，并且比对照淋巴管更慢地排出溶质。暴露于模拟肥胖的脂肪细胞的CM不影响淋巴管。当暴露于模拟肥胖时，富含脂肪细胞凝胶中的淋巴管没有表现出更差的引流功能。结论：肥胖相关炎症、缺氧和高脂血症的联合作用直接作用于LECs，从而损害淋巴溶质排泄。令人惊讶的是，脂肪细胞可能在预防肥胖相关疾病中发挥保护作用，这些疾病会损害淋巴溶质排泄。补充信息：在线版本包含补充资料，提供地址为10.1007/s12195-024-00840-z。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.