Int J Stem Cells.  2017 May;10(1):1-11. 10.15283/ijsc17024.

From Bench to Market: Preparing Human Pluripotent Stem Cells Derived Cardiomyocytes for Various Applications

• Moon SH
• Bae D
• Jung TH
• Chung EB
• Jeong YH
• Park SJ
• Chung HM

• KMID: 2384596
• DOI: http://doi.org/10.15283/ijsc17024

Abstract

Human cardiomyocytes (CMs) cease to proliferate and remain terminally differentiated thereafter, when humans reach the mid-20s. Thus, any damages sustained by myocardium tissue are irreversible, and they require medical interventions to regain functionality. To date, new surgical procedures and drugs have been developed, albeit with limited success, to treat various heart diseases including myocardial infarction. Hence, there is a pressing need to develop more effective treatment methods to address the increasing mortality rate of the heart diseases. Functional CMs are not only an important in vitro cellular tool to model various types of heart diseases for drug development, but they are also a promising therapeutic agent for cell therapy. However, the limited proliferative capacity entails difficulties in acquiring functional CMs in the scale that is required for pathological studies and cell therapy development. Stem cells, human pluripotent stem cells (hPSCs) in particular, have been considered as an unlimited cellular source for providing functional CMs for various applications. Notable progress has already been made: the first clinical trials of hPSCs derived CMs (hPSC-CMs) for treating myocardial infarction was approved in 2015, and their potential use in disease modeling and drug discovery is being fully explored. This concise review gives an account of current development of differentiation, purification and maturation techniques for hPSC-CMs, and their application in cell therapy development and pharmaceutical industries will be discussed with the latest experimental evidence.

Keyword

Human pluripotent stem cell; Cardiomyocytes; Cell therapy; Drug discovery; Disease modeling

MeSH Terms

Cell- and Tissue-Based Therapy
Drug Discovery
Drug Industry
Heart Diseases
Humans*
In Vitro Techniques
Mortality
Myocardial Infarction
Myocardium
Myocytes, Cardiac*
Pluripotent Stem Cells*
Stem Cells

Figure

• 

  Fig. 1 Representative differentiation methods for hPSC-CMs. Differentiation strategies for hPSC-CMs can largely be divided into three most commonly used methods: via EB formation, 2D monolayer differentiation and co-culture system. The first two methods require supplementation of differentiation inducers (growth factors and small molecules) whereas these factors are redundant in the END-2 co-culture system. Abbreviations: EB: embryoid body, BMP4: bone morphogenetic protein 4.

• 

  Fig. 2 Stage-specific differentiation inducers and cell characteristics. hPSC-CMs differentiation takes place sequentially as shown above. The cells exhibit distinct phenotypic and genotypic characteristics pertaining to a specific stage, where a combination of differentiation inducers is supplemented to proceed to the next stage. The final stage of the differentiation involves maturation of nascent and immature CMs.

• 

  Fig. 3 Purification and maturation for hPSC-CMs. hPSC-CMs are enriched following the differentiation because the procedure inevitably yields by-products. The purified hPSC-CMs exhibit immature characteristics, as the differentiation methods are often completed 20–30 days after the initiation. Purification and maturation are prerequisite procedures for subsequent applications of hPSC-CMs. Abbreviations: FACs: fluorescence activated cell sorting, MACs: magnetic activated cell sorting.

Reference

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