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Review
. 2018 Apr 24:5:110.
doi: 10.3389/fmed.2018.00110. eCollection 2018.

Engineering Scalable Manufacturing of High-Quality Stem Cell-Derived Cardiomyocytes for Cardiac Tissue Repair

Kaitlin K Dunn  1 , Sean P Palecek  1
Affiliations
Review

Engineering Scalable Manufacturing of High-Quality Stem Cell-Derived Cardiomyocytes for Cardiac Tissue Repair

Kaitlin K Dunn et al. Front Med (Lausanne). .

Abstract

Recent advances in the differentiation and production of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) have stimulated development of strategies to use these cells in human cardiac regenerative therapies. A prerequisite for clinical trials and translational implementation of hPSC-derived CMs is the ability to manufacture safe and potent cells on the scale needed to replace cells lost during heart disease. Current differentiation protocols generate fetal-like CMs that exhibit proarrhythmogenic potential. Sufficient maturation of these hPSC-derived CMs has yet to be achieved to allow these cells to be used as a regenerative medicine therapy. Insights into the native cardiac environment during heart development may enable engineering of strategies that guide hPSC-derived CMs to mature. Specifically, considerations must be made in regard to developing methods to incorporate the native intercellular interactions and biomechanical cues into hPSC-derived CM production that are conducive to scale-up.

Keywords: cardiac repair; cardiomyocyte; cell manufacturing; coculture; differentiation; human pluripotent stem cells; maturation; regenerative medicine.

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Figures

Figure 1
Figure 1
Comparison of select directed differentiation protocols for differentiating human pluripotent stem cells to cardiomyocytes (CMs).
Figure 2
Figure 2
Comparison of human pluripotent stem cell (hPSC)-derived CMs and adult CMs demonstrating the structural and organizational changes during maturation.
Figure 3
Figure 3
Schematic illustrating types of intercellular interactions and their scalability for inclusion into large-scaling manufacturing.
Figure 4
Figure 4
Different strategies to introduce intercellular interactions during human pluripotent stem cell-derived cardiomyocyte manufacturing.
See this image and copyright information in PMC

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