Abstract
Transplantation of human pluripotent stem cell (hPSCs)-derived cardiomyocytes for the treatment of heart failure is a promising therapy. In order to implement this therapy requiring numerous cardiomyocytes, substantial production of hPSCs followed by cardiac differentiation seems practical. Conventional methods of culturing hPSCs involve using a 2D culture monolayer that hinders the expansion of hPSCs, thereby limiting their productivity. Advanced culture of hPSCs in 3D aggregates in the suspension overcomes the limitations of 2D culture and attracts immense attention. Although the hPSC production needs to be suitable for subsequent cardiac differentiation, many studies have independently focused on either expansion of hPSCs or cardiac differentiation protocols. In this review, we summarize the recent approaches to expand hPSCs in combination with cardiomyocyte differentiation. A comparison of various suspension culture methods and future prospects for dynamic culture of hPSCs are discussed in this study. Understanding hPSC characteristics in different models of dynamic culture helps to produce numerous cells that are useful for further clinical applications.
Highlights
Cardiovascular diseases are the leading cause of mortality worldwide
Production of cardiomyocytes by differentiation from human pluripotent stem cells has gained immense attention. hPSCs, including human embryonic stem cells [3] and human induced pluripotent stem cells [4], have the capability to differentiate into many cell lineages, such as cardiac progenitors, cardiomyocytes, and endothelial cells
Cardiomyocytes derived from hPSCs are a promising cell source for cell transplantation therapy in heart failures as well as drug discovery and disease modeling for cardiac diseases; as discussed in this review, there are several technical barriers to achieve necessary number and quality of cardiomyocytes
Summary
Cardiovascular diseases are the leading cause of mortality worldwide. Angina and myocardial infarction known as heart attack is most frequent and occurs when the blood flow to the heart is obstructed, thereby damaging the heart muscles. HPSCs, including human embryonic stem cells (hESCs) [3] and human induced pluripotent stem cells (hiPSCs) [4], have the capability to differentiate into many cell lineages, such as cardiac progenitors, cardiomyocytes, and endothelial cells. Production of cardiomyocytes by differentiation from human pluripotent stem cells (hPSCs) has gained immense attention. These cells are reported to be necessary for formation of cardiac muscle tissue in vivo. Cardiomyocytes derived from hPSCs can be transplanted to the patient’s body and applied as a model for cardiac drug screening and disease modeling. We include discussing the pros and cons of each model and propose the future prospect toward achieving sustainable and scalable, highly efficient production of cardiomyocytes for use in clinical applications
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