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Review
. 2023 Jul 6:14:1213959.
doi: 10.3389/fphys.2023.1213959. eCollection 2023.

Building blocks of microphysiological system to model physiology and pathophysiology of human heart

Hanna Vuorenpää  1   2   3 , Miina Björninen  1   2   3 , Hannu Välimäki  1   4 , Antti Ahola  1   5 , Mart Kroon  1   6 , Laura Honkamäki  1   7 , Jussi T Koivumäki  1   5 , Mari Pekkanen-Mattila  1   8
Affiliations
Review

Building blocks of microphysiological system to model physiology and pathophysiology of human heart

Hanna Vuorenpää et al. Front Physiol. .

Abstract

Microphysiological systems (MPS) are drawing increasing interest from academia and from biomedical industry due to their improved capability to capture human physiology. MPS offer an advanced in vitro platform that can be used to study human organ and tissue level functions in health and in diseased states more accurately than traditional single cell cultures or even animal models. Key features in MPS include microenvironmental control and monitoring as well as high biological complexity of the target tissue. To reach these qualities, cross-disciplinary collaboration from multiple fields of science is required to build MPS. Here, we review different areas of expertise and describe essential building blocks of heart MPS including relevant cardiac cell types, supporting matrix, mechanical stimulation, functional measurements, and computational modelling. The review presents current methods in cardiac MPS and provides insights for future MPS development with improved recapitulation of human physiology.

Keywords: biomaterials; cardiac modeling; co-cultures; environmental control; imaging; in silico; in vitro; microphysiological systems.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Building blocks of cardiac microphysiological systems (MPS). We cover the topics that fall under these three main categories in the review.
FIGURE 2
FIGURE 2
Assessment of hiPSC-CM and EHT maturity in MPS. Human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM), engineered heart tissue (EHT), microphysiological systems (MPS).
FIGURE 3
FIGURE 3
(A) main cell types and their functions in human heart, (B) representation of a method to innervate and vascularize heart MPS. Created with BioRender.com.
FIGURE 4
FIGURE 4
Commonly used mechanical stimulation methods for cardiac maturation of hiPSC-CM and important considerations when implementing electrical stimulation with or without mechanical stimulation. Created with BioRender.com.
FIGURE 5
FIGURE 5
A functional scheme of a cardiac MPS. Various stimuli affect the cell block located in the rapid section, where the membrane potential gives rise to intracellular calcium flux, which in turn starts the mechanical contraction. The immediate functional responses can be recorded by measuring membrane potential, intracellular calcium or contractility via various in situ methods. (Bio-)chemical responses can typically be performed in-line, on-line or off-line.
FIGURE 6
FIGURE 6
Challenges and opportunities related to the MPS building blocks and their integration.
See this image and copyright information in PMC

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