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Review
. 2017 Feb:16:30-40.
doi: 10.1016/j.ebiom.2017.01.029. Epub 2017 Jan 27.

Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise

Affiliations
Review

Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise

Robin Duelen et al. EBioMedicine. 2017 Feb.

Abstract

Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine. Human pluripotent stem cells (PSCs) have emerged as attractive cell source to obtain cardiomyocytes (CMs), with potential applications, including drug discovery and toxicity screening, disease modelling and innovative cell therapies. Lessons from embryology offered important insights into the development of stem cell-derived CMs. However, the generation of a CM population, uniform in cardiac subtype, adult maturation and functional properties, is highly recommended. Moreover, hurdles regarding tumorigenesis, graft cell death, immune rejection and arrhythmogenesis need to be overcome in clinical practice. Here we highlight the recent progression in PSC technologies for the regeneration of injured heart. We review novel strategies that might overcome current obstacles in heart regenerative medicine, aiming at improving cell survival and functional integration after cell transplantation.

Keywords: Embryonic cardiomyogenesis; Heart regeneration; Human pluripotent stem cell; Stem cell-based therapy; Stem cell-derived exosome.

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Figures

Fig. 1
Fig. 1
Mouse gastrulation. Early primitive streak (PS) formation at 6.5 days after fertilisation. The posterior region of the PS coexpresses Brachyury and HoxB1/Evx1. The anterior region coexpresses Brachyury and Foxa2/Goosecoid. Epiblast cells enter the anterior PS (black arrows on top of the embryo) and generate cardiac mesoderm.
Fig. 2
Fig. 2
Potential cell sources for heart regeneration therapy. Embryonic (ESC) and induced pluripotent stem cell (iPSC) populations as well as adult stem cell types have been shown to improve cardiac morphological and functional characteristics via differentiation towards cardiomyocytes (CMs), smooth muscle cells (SMCs) and endothelial cells (ECs) or through paracrine effects.
Fig. 3
Fig. 3
Stem cell-based strategies for cardiac regeneration after heart disease. Multiple techniques to improve morphological and electromechanical properties of the diseased heart: (1) In vitro cardiac differentiation of different stem cell types. (2) Tissue engineering approaches combining cells with biomaterials to design in vitro cardiac patches or injectable scaffolds for transplantation into the infarcted heart area. (3) Cell- and gene-based strategies secreting cytokines, growth factors and microRNAs to promote cardiac regeneration. (4) Stem-cell derived exosomes as an innovative cell-free therapy in heart regenerative medicine.

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