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Review
. 2016 Jul;1863(7 Pt B):1829-38.
doi: 10.1016/j.bbamcr.2015.11.005. Epub 2015 Nov 11.

Maturation status of sarcomere structure and function in human iPSC-derived cardiac myocytes

Fikru B Bedada  1 , Matthew Wheelwright  1 , Joseph M Metzger  2
Affiliations
Review

Maturation status of sarcomere structure and function in human iPSC-derived cardiac myocytes

Fikru B Bedada et al. Biochim Biophys Acta. 2016 Jul.

Abstract

Human heart failure due to myocardial infarction is a major health concern. The paucity of organs for transplantation limits curative approaches for the diseased and failing adult heart. Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) have the potential to provide a long-term, viable, regenerative-medicine alternative. Significant progress has been made with regard to efficient cardiac myocyte generation from hiPSCs. However, directing hiPSC-CMs to acquire the physiological structure, gene expression profile and function akin to mature cardiac tissue remains a major obstacle. Thus, hiPSC-CMs have several hurdles to overcome before they find their way into translational medicine. In this review, we address the progress that has been made, the void in knowledge and the challenges that remain. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Keywords: Differentiation; Heart; Maturation; Stem cells; Troponin.

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Conflict of interest statement

Conflict of interest

None

Figures

Figure 1
Figure 1. Differentiation of hiPSC-CMs
Schematic of the differentiation protocol for hiPSC-CMs as described recently [7, 13].
Figure 2
Figure 2. Developmental progression of cardiac myocytes
The pyramid depicts the developmental transition from fetal stages to fully mature rod-shaped adult myocytes, and the recurrence of the fetal program during heart disease.
Figure 3
Figure 3. Structural organization of hiPSC-CMs
Schematic of hiPSC-CMs repopulating a biological matrix aligned and displaying sarcomere organization (right panel) compared with those cultured in the absence of biological matrix (left panel). Calibration bar is 50 µm.
Figure 4
Figure 4. Overview of experimental flow utilizing hiPSC-CMs
Functionality of hiPSCs, having been differentiated into cardiac myocytes, is characterized in terms of electrical activity, calcium cycling, and contractility. Fully characterized hiPSC-CMs are used for diverse applications including disease modeling, drug discovery, and therapeutic applications.
See this image and copyright information in PMC

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