Blood and Lymphatic Vasculatures On-Chip Platforms and Their Applications for Organ-Specific In Vitro Modeling
Aria R Henderson1, Hyoann Choi2, Esak Lee1
1Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
Insights
Accurate models of the cardiovascular and lymphatic systems are crucial for understanding diseases. Three-dimensional microfluidic devices offer promising platforms for studying these complex vascular networks in vitro.
Area of Science:
- Physiology
- Biomedical Engineering
- Pathology
Background:
- The human circulatory system comprises distinct cardiovascular and lymphatic systems, essential for nutrient/waste transport, fluid homeostasis, and immune response.
- Both systems exhibit organ-specific variations and play vital roles in maintaining overall homeostasis.
- Dysfunction in either vasculature can lead to severe, life-threatening diseases.
Purpose of the Study:
- To review the heterogeneity of blood and lymphatic vessels.
- To explore current in vitro models, particularly three-dimensional (3D) microfluidic devices, for studying vascular physiology and pathology.
- To discuss organ-specific vascular features and disease implications, focusing on the gut and brain.
Main Methods:
- Literature review of vascular heterogeneity and in vitro modeling techniques.
- Analysis of organ-specific vascular functions and pathologies in the gut and brain.
- Emphasis on the application of on-chip (microfluidic) technologies for disease modeling.
Main Results:
- Vascular heterogeneity necessitates advanced in vitro models that replicate physiological conditions like flow, extracellular matrix, and biochemical gradients.
- Three-dimensional microfluidic devices show promise for accurately modeling in vivo vascular environments.
- Organ-specific vascular differences impact disease manifestation and progression.
Conclusions:
- Advanced in vitro models, especially 3D microfluidics, are vital for studying complex vascular systems and associated diseases.
- Understanding organ-specific vascular characteristics is key to developing targeted therapeutic strategies.
- On-chip techniques provide powerful tools for disease modeling and research.
Abstract:
The human circulatory system is divided into two complementary and different systems, the cardiovascular and the lymphatic system. The cardiovascular system is mainly concerned with providing nutrients to the body via blood and transporting wastes away from the tissues to be released from the body. The lymphatic system focuses on the transport of fluid, cells, and lipid from interstitial tissue spaces to lymph nodes and, ultimately, to the cardiovascular system, as well as helps coordinate interstitial fluid and lipid homeostasis and immune responses. In addition to having distinct structures from each other, each system also has organ-specific variations throughout the body and both systems play important roles in maintaining homeostasis. Dysfunction of either system leads to devastating and potentially fatal diseases, warranting accurate models of both blood and lymphatic vessels for better studies. As these models also require physiological flow (luminal and interstitial), extracellular matrix conditions, dimensionality, chemotactic biochemical gradient, and stiffness, to better reflect in vivo, three dimensional (3D) microfluidic (on-a-chip) devices are promising platforms to model human physiology and pathology. In this review, we discuss the heterogeneity of both blood and lymphatic vessels, as well as current in vitro models. We, then, explore the organ-specific features of each system with examples in the gut and the brain and the implications of dysfunction of either vasculature in these organs. We close the review with discussions on current in vitro models for specific diseases with an emphasis on on-chip techniques.
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