LPS) to the liver, perturbing its homeostatic balance and impacting metastatic growth, and possibly drug efficacy and/or toxicity.
This would take form as (ii) a complex immuno-component gut module wherein the barrier function is compromised sending inflammatory signals ( e.g. (Ci) A desirable feature, would be integrating a gut directly to the liver with bidirectional ‘blood flow’. hepatocytes, KCs, LSECs, and HSCs) with physiologically relevant flow parameters.
NATIVA LIVER COMPLEX FULL
(ii) The liver module should comprise a full complement of resident hepatic cells ( i.e. Tumor cells would transit through micro-channels that are interconnected to a (Bi) liver where they colonize and eventually outgrow into metastatic lesions. Integration with a liver module could occur (ii) via introduction of patient-derived CTCs or (iii) with a complex, multicellular primary tumor organoid module incorporating stromal and ECM components.
(Ai) Examples of primary tumors that can metastasize to the liver. The left depicts organ systems, while the right illustrates fabricated MPS modules. Schematic of a prospective integrated model of cancer metastasis to the liver. Liver metastasis Metastasis-On-A-Chip Metastatic microenvironment Metastatic models Microphysiological system.Ĭopyright © 2020 Elsevier Ltd. In addition, inflammatory organs and the immune system can be incorporated into these multi-organ systems to probe the effects on tumor behavior and cancer treatments. Herein, we discuss extending this concept to tumor metastases by integrating complex models of the primary tumor with the liver metastatic environment.
To examine the influence of one organ on the function of other tissues, microphysiological systems are being linked. However, neither the tumor nor the liver exist in an isolated tissue situation, having to function within a complete body and respond to systemic events as well as those in other organs. These microphysiological systems have provided unexpected and powerful insights into the tumor cell biology of metastasis. The use of biologically and cellularly complex liver tissue systems have shown that tumor cell behavior and therapeutic responses are modulated within the liver microenvironment and in ways distinct from the behaviors in the primary locations. The liver is the most commonly involved organ in metastases from a wide variety of solid tumors.
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