Microfluidic-Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and Disease.
Microfluidic-Based Reconstitution of Functional Lymphatic Microvasculature: Elucidating the Role of Lymphatics in Health and Disease.
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DOI：
10.1002/advs.202302903
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发表时间：
2024-02
期刊：
影响因子：
15.1
通讯作者：
Kamm, Roger D.
中科院分区：
文献类型：
--
作者：
Serrano, Jean C.;Gillrie, Mark R.;Li, Ran;Ishamuddin, Sarah H.;Moeendarbary, Emad;Kamm, Roger D.
由于几十年的研究和细胞生物学和组织工程学的大量进展，人们对血液微血管及其在健康和疾病中的功能作用的认识已经显著增长；然而，淋巴管(次级血管系统)没有得到类似的关注，部分原因是缺乏模拟其病理生理功能的相关体外模型。在这里，采用了一种基于微流体的方法来实现对生长因子和间质流动的精确控制，这些生长因子和间质流动驱动着体内毛细淋巴管的生长(淋巴管生成)。具有体内相似形态的工程化芯片上淋巴管展示了组织规模的功能，间质蛋白质和分子的排泄率与体内标准相当。对潜在运输现象的计算和尺度分析阐明了三维几何结构和淋巴管内皮细胞在概括生理引流中的关键作用。最后，经过改造的芯片上的淋巴管能够研究淋巴管-免疫相互作用，揭示淋巴管通过类似于体内病理事件的趋化信号招募免疫细胞的炎症驱动反应。这个芯片上的淋巴学平台允许询问各种淋巴生物学功能，以及筛选基于淋巴的疗法，例如蛋白质疗法的间质吸收和用于癌症治疗的淋巴免疫调节。通过实施微流控技术，研究人员成功地在芯片上模拟了体内淋巴的生长和功能。这一突破使对淋巴生理引流的详细研究和对淋巴-免疫相互作用的机械性洞察成为可能，从而使基于淋巴的治疗方法的高级筛选成为可能。
The knowledge of the blood microvasculature and its functional role in health and disease has grown significantly attributable to decades of research and numerous advances in cell biology and tissue engineering; however, the lymphatics (the secondary vascular system) has not garnered similar attention, in part due to a lack of relevant in vitro models that mimic its pathophysiological functions. Here, a microfluidic‐based approach is adopted to achieve precise control over the biological transport of growth factors and interstitial flow that drive the in vivo growth of lymphatic capillaries (lymphangiogenesis). The engineered on‐chip lymphatics with in vivo‐like morphology exhibit tissue‐scale functionality with drainage rates of interstitial proteins and molecules comparable to in vivo standards. Computational and scaling analyses of the underlying transport phenomena elucidate the critical role of the three‐dimensional geometry and lymphatic endothelium in recapitulating physiological drainage. Finally, the engineered on‐chip lymphatics enabled studies of lymphatic‐immune interactions that revealed inflammation‐driven responses by the lymphatics to recruit immune cells via chemotactic signals similar to in vivo, pathological events. This on‐chip lymphatics platform permits the interrogation of various lymphatic biological functions, as well as screening of lymphatic‐based therapies such as interstitial absorption of protein therapeutics and lymphatic immunomodulation for cancer therapy. By implementing microfluidic techniques, researchers successfully mimic in vivo lymphatic growth and function on‐chip. This breakthrough permits detailed study on lymphatic physiological drainage, and mechanistic insights into lymphatic‐immune interactions, thereby enabling advanced screening of lymphatic‐based therapeutics.
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影响因子：
9.8
作者：
Karaman, Sinem;Buschle, Dorina;Proulx, Steven T.
通讯作者：
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影响因子：
32.4
作者：
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通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
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DOI：
10.1007/978-1-4939-8712-2_2
发表时间：
2018-01-01
期刊：
LYMPHANGIOGENESIS: METHODS AND PROTOCOLS
影响因子：
--
作者：
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通讯作者：
Harvey, Natasha L.
DOI：
10.1073/pnas.86.14.5385
发表时间：
1989-07-01
影响因子：
11.1
作者：
CHARY, SR;JAIN, RK
通讯作者：
JAIN, RK