Modeling lymphangiogenesis: Pairing in vitro and in vivo metrics

IF 1.9 4区 医学 Q3 HEMATOLOGY
Aileen C. Suarez, Jennifer H. Hammel, Jennifer M. Munson
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引用次数: 4

Abstract

Lymphangiogenesis is the mechanism by which the lymphatic system develops and expands new vessels facilitating fluid drainage and immune cell trafficking. Models to study lymphangiogenesis are necessary for a better understanding of the underlying mechanisms and to identify or test new therapeutic agents that target lymphangiogenesis. Across the lymphatic literature, multiple models have been developed to study lymphangiogenesis in vitro and in vivo. In vitro, lymphangiogenesis can be modeled with varying complexity, from monolayers to hydrogels to explants, with common metrics for characterizing proliferation, migration, and sprouting of lymphatic endothelial cells (LECs) and vessels. In comparison, in vivo models of lymphangiogenesis often use genetically modified zebrafish and mice, with in situ mouse models in the ear, cornea, hind leg, and tail. In vivo metrics, such as activation of LECs, number of new lymphatic vessels, and sprouting, mirror those most used in vitro, with the addition of lymphatic vessel hyperplasia and drainage. The impacts of lymphangiogenesis vary by context of tissue and pathology. Therapeutic targeting of lymphangiogenesis can have paradoxical effects depending on the pathology including lymphedema, cancer, organ transplant, and inflammation. In this review, we describe and compare lymphangiogenic outcomes and metrics between in vitro and in vivo studies, specifically reviewing only those publications in which both testing formats are used. We find that in vitro studies correlate well with in vivo in wound healing and development, but not in the reproductive tract or the complex tumor microenvironment. Considerations for improving in vitro models are to increase complexity with perfusable microfluidic devices, co-cultures with tissue-specific support cells, the inclusion of fluid flow, and pairing in vitro models of differing complexities. We believe that these changes would strengthen the correlation between in vitro and in vivo outcomes, giving more insight into lymphangiogenesis in healthy and pathological states.

Abstract Image

模拟淋巴管生成:配对体外和体内指标
淋巴管生成是淋巴系统发展和扩张新血管的机制,促进液体排泄和免疫细胞运输。研究淋巴管生成的模型对于更好地理解潜在的机制以及识别或测试针对淋巴管生成的新治疗剂是必要的。在淋巴文献中,已经建立了多种模型来研究体外和体内淋巴管生成。在体外,淋巴管生成可以以不同的复杂性建模,从单层到水凝胶再到外植体,具有表征淋巴内皮细胞(LECs)和血管的增殖、迁移和发芽的共同指标。相比之下,体内淋巴管生成模型通常使用转基因斑马鱼和小鼠,小鼠的耳朵、角膜、后腿和尾巴都有原位模型。体内指标,如LECs的激活、新淋巴管的数量和发芽,反映了体外最常用的指标,并增加了淋巴管增生和引流。淋巴管生成的影响因组织和病理的不同而不同。淋巴管生成的治疗靶向可能会产生矛盾的效果,这取决于病理,包括淋巴水肿、癌症、器官移植和炎症。在这篇综述中,我们描述并比较了体外和体内研究的淋巴管生成结果和指标,特别回顾了使用两种测试格式的出版物。我们发现,体外研究与体内伤口愈合和发育密切相关,但与生殖道或复杂的肿瘤微环境无关。改进体外模型的考虑因素是增加可灌注微流体装置的复杂性,与组织特异性支持细胞共培养,包括流体流动,以及不同复杂性的体外模型配对。我们相信这些变化将加强体外和体内结果之间的相关性,使我们更深入地了解健康和病理状态下的淋巴管生成。
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来源期刊
Microcirculation
Microcirculation 医学-外周血管病
CiteScore
5.00
自引率
4.20%
发文量
43
审稿时长
6-12 weeks
期刊介绍: The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.
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