Three-dimensional cardiac models: a pre-clinical testing platform

Biochemical Society Transactions, vol. 52, pp. 1045–1059

Abstract

Major advancements in human pluripotent stem cell (hPSC) technology over recent years have yielded valuable tools for cardiovascular research. Multi-cell type 3-dimensional (3D) cardiac models in particular, are providing complementary approaches to animal studies that are better representatives than simple 2-dimensional (2D) cultures of differentiated hPSCs. These human 3D cardiac models can be broadly divided into two categories; namely those generated through aggregating pre-differentiated cells and those that form self-organizing structures during their in vitro differentiation from hPSCs. These models can either replicate aspects of cardiac development or enable the examination of interactions among constituent cell types, with some of these models showing increased maturity compared with 2D systems. Both groups have already emerged as physiologically relevant pre-clinical platforms for studying heart disease mechanisms, exhibiting key functional attributes of the human heart. In this review, we describe the different cardiac organoid models derived from hPSCs, their generation methods, applications in cardiovascular disease research and use in drug screening. We also address their current limitations and challenges as pre-clinical testing platforms and propose potential improvements to enhance their efficacy in cardiac drug discovery.

Authors 4

1. Eline Groen Aachen 1Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   1Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands

2. Christine L. Mummery Aachen 1Department of Anatomy and Embryology 2The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW)

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   1Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands

   2The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, 2300RC Leiden, The Netherlands

3. Loukia Yiangou corresponding Aachen 1Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   1Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands

4. Richard P. Davis corresponding Aachen 1Department of Anatomy and Embryology 2The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW)

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   1Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands

   2The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, 2300RC Leiden, The Netherlands