Geometrical model of lobular structure and its importance for the liver perfusion analysis

A convenient geometrical description of the microvascular network is necessary for computationally efficient mathematical modelling of liver perfusion, metabolic and other physiological processes. The tissue models currently used are based on the generally accepted schematic structure of the parenchyma at the lobular level, assuming its perfect regular structure and geometrical symmetries. Hepatic lobule, portal lobule, or liver acinus are considered usually as autonomous functional units on which particular physiological problems are studied. We propose a new periodic unit—the liver representative periodic cell (LRPC) and establish its geometrical parametrization. The LRPC is constituted by two portal lobulae, such that it contains the liver acinus as a substructure. As a remarkable advantage over the classical phenomenological modelling approaches, the LRPC enables for multiscale modelling based on the periodic homogenization method. Derived macroscopic equations involve so called effective medium parameters, such as the tissue permeability, which reflect the LRPC geometry. In this way, mutual influences between the macroscopic phenomena, such as inhomogeneous perfusion, and the local processes relevant to the lobular (mesoscopic) level are respected. The LRPC based model is intended for its use within a complete hierarchical model of the whole liver. Using the Double-permeability Darcy model obtained by the homogenization, we illustrate the usefulness of the LRPC based modelling to describe the blood perfusion in the parenchyma.

Patient-specific microphysiology systems are likely to become a crucial aspect of translational research and precision medicine

Basic biomedical research, drug discovery and development pipelines address unique "contexts of usage" that include such requirements as high-throughput experimentation, information content, functional biological complexity, and/or clinically relevant disease progression recapitulation. The model was created to more accurately recapitulate key features of the liver acinus structure and functions, including both physical and biochemical environmental cues, in order to help scientists better understand disease mechanisms, identify biomarkers linked to those mechanisms, and better predict drug response and ADME. HBL-MPS liver MPS models, which are designed to optimally mimic the liver acinus as a stand-alone liver model or in conjunction with other organs, are now preferred. Current HBL-MPS models have shown the capability to examine multicellular and temporal-spatial physiological and pathological heterogeneity inside the liver acinus. These MPS models have been utilized to look at crucial disease development pathways connected with NAFLD, type 2 diabetes, and liver metastases. Mature liver acinus cells generated from patient-specific iPSCs provide a significant impediment to full realization of the MPS 'potential capability. Organoid-MPS develop into distinct autologous liver cell types, whereas Structured-MPS are positioned or bioprinted within microfluidic devices. If this project works, Organoid-MPS and/or Structured-MPS might be applied in precision medicine applications. Patient-specific MPS used in preclinical investigations have the capacity to predict clinical response, helping to optimize the selection of patient groups for clinical trials.Despite the fact that MPS is predicted to have a large influence on the future of precision medicine, there are still many barriers to overcome. Also, lineage differentiation efficacy differs between donor lines and individual experiments, resulting in a heterogeneous population of various cell types. However, patient-specific MPS is likely to become a crucial aspect of translational research and precision medicine, considering the rate of technology developments and the availability of clinical validation trials.

A glass-based, continuously zonated and vascularized human liver acinus microphysiological system (vLAMPS) designed for experimental modeling of diseases and ADME/TOX

We developed a glass based, vascularized human biomimetic liver MPS recreating oxygen zonation present in the liver acinus.