Engineering Lymphangiogenesis-On-Chip: The Independent and Cooperative Regulation by Biochemical Factors, Gradients, and Interstitial Fluid Flow.
Engineering Lymphangiogenesis-On-Chip: The Independent and Cooperative Regulation by Biochemical Factors, Gradients, and Interstitial Fluid Flow.
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芯片上工程淋巴管生成：生化因素、梯度和间质液流的独立和协同调节。
DOI：
10.1002/adbi.202400031
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发表时间：
2024
期刊：
影响因子：
3.7
通讯作者：
Jain,Abhishek
中科院分区：
文献类型：
--
作者：
Tronolone,JamesJ;Mohamed,Nadin;Jain,Abhishek
尽管淋巴管生成在发育过程中以及在与组织再生、免疫和癌症有关的几种疾病中起着至关重要的作用，但相对于血管生成，了解这一过程的工具明显较少。虽然已经有一个主要的激增，在微生理系统的血管生成建模，他们还没有严格的优化或标准化，使淋巴管生成的动态重建。在这里，淋巴管生成芯片（L-Chip）被工程化，其中新的芽形成和成熟取决于间质流的施加，生长因子梯度和用生长因子预处理内皮细胞。L-Chip揭示了淋巴管生成的这些机械和生物化学决定因素的独立和组合效应，从而最终导致芽从母血管中出现并在4天内成熟为长度达1 mm的管状结构，超过了现有技术。此外，当解剖用于引发和促进淋巴管生成的预处理混合物和生长因子混合物的构成时，发现内聚糖（ESM-1）导致相对于血管生成更占优势的淋巴管生成。因此，L-Chip为淋巴管生成特异性微流体检测的标准化提供了基础，并加速了与血管生成同等的基础和转化科学。
Despite the crucial role of lymphangiogenesis during development and in several diseases with implications for tissue regeneration, immunity, and cancer, there are significantly fewer tools to understand this process relative to angiogenesis. While there has been a major surge in modeling angiogenesis with microphysiological systems, they have not been rigorously optimized or standardized to enable the recreation of the dynamics of lymphangiogenesis. Here, a Lymphangiogenesis‐Chip (L‐Chip) is engineered, within which new sprouts form and mature depending upon the imposition of interstitial flow, growth factor gradients, and pre‐conditioning of endothelial cells with growth factors. The L‐Chip reveals the independent and combinatorial effects of these mechanical and biochemical determinants of lymphangiogenesis, thus ultimately resulting in sprouts emerging from a parent vessel and maturing into tubular structures up to 1 mm in length within 4 days, exceeding prior art. Further, when the constitution of the pre‐conditioning cocktail and the growth factor cocktail used to initiate and promote lymphangiogenesis are dissected, it is found that endocan (ESM‐1) results in more dominant lymphangiogenesis relative to angiogenesis. Therefore, The L‐Chip provides a foundation for standardizing the microfluidics assays specific to lymphangiogenesis and for accelerating its basic and translational science at par with angiogenesis.
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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
影响因子：
5.8
作者：
Frenkel, Nicola;Poghosyan, Susanna;Hagendoorn, Jeroen
通讯作者：
Hagendoorn, Jeroen
影响因子：
20.3
作者：
Kunstfeld, R;Hirakawa, S;Detmar, M
通讯作者：
Detmar, M
影响因子：
14
作者：
Boussommier-Calleja A;Atiyas Y;Haase K;Headley M;Lewis C;Kamm RD
通讯作者：
Kamm RD
在高通量的体外平台中灌注3D血管生成。
影响因子：
9.8
作者：
van Duinen V;Zhu D;Ramakers C;van Zonneveld AJ;Vulto P;Hankemeier T
通讯作者：
Hankemeier T