Microscale Engineering of Blind-Ended Lymphatic Capillaries
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Date
2024-12
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The Ohio State University
Abstract
The lymphatic system plays a key role within the body by regulating tissue-fluid homeostasis and coordinating immune responses [1]. This system is comprised of three sections: 1) lymph nodes, 2) collecting lymphatic vessels, and initial lymphatic vessels [1]. The initial lymphatic vessels (also known as lymphatic capillaries) use pressure gradients to absorb fluid and solutes from the surrounding tissue and then transport it along to the collecting vessels [2]. These lymphatic vessels are important in the context of cancer metastasis as they are known to be used as passages for cancer cells to move easily throughout the body [3]. To do so, solid tumors, such as those in breast cancer are known to indirectly increase the fluid pressure in the tumor microenvironment (TME) and secrete growth factors to encourage lymphatic vessel growth, known as lymphangiogenesis, towards the tumor [3], [4]. Lymphangiogenesis is believed to also be impacted by the increase in transvascular fluid flow into the vessel from the increased pressure [5]. One proposed hypothesis is that inhibiting lymphangiogenesis will prevent cancer cell dissemination through the lymphatics vasculature [6]. However, these capillary lymphatics are difficult study both in vivo and in vitro due in part to their thin walls, small diameter, and the fact that key lymphatic biomarkers were only discovered in the past 20 years [7], [8]. To better study these vessels, I contributed to the development of a 3D microfluidic device that is capable of recapitulating functional capillary lymphatic vessels and the microenvironment in which they exist. This model was used to study how local fluid mechanical forces and a known lymphangiogenic chemokine, vascular endothelial growth factor C (VEGF-C), co-directs lymphangiogenesis in comparison to static conditions.
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Keywords
Microdevice, Capillary Lymphatic, Lymphangiogenesis, Microfluidics