A Concise Review on Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Personalized Regenerative Medicine
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A Concise Review on Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Personalized Regenerative Medicine Pallavi Pushp 1,2 & Diogo E. S. Nogueira 3 & Carlos A. V. Rodrigues 3 & Frederico C. Ferreira 3 & Joaquim M. S. Cabral 3 & Mukesh Kumar Gupta 2 Accepted: 16 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The induced pluripotent stem cells (iPSCs) are derived from somatic cells by using reprogramming factors such as Oct4, Sox2, Klf4, and c-Myc (OSKM) or Oct4, Sox2, Nanog and Lin28 (OSNL). They resemble embryonic stem cells (ESCs) and have the ability to differentiate into cell lineage of all three germ-layer, including cardiomyocytes (CMs). The CMs can be generated from iPSCs by inducing embryoid bodies (EBs) formation and treatment with activin A, bone morphogenic protein 4 (BMP4), and inhibitors of Wnt signaling. However, these iPSC-derived CMs are a heterogeneous population of cells and require purification and maturation to mimic the in vivo CMs. The matured CMs can be used for various therapeutic purposes in regenerative medicine by cardiomyoplasty or through the development of tissue-engineered cardiac patches. In recent years, significant advancements have been made in the isolation of iPSC and their differentiation, purification, and maturation into clinically usable CMs. Newer small molecules have also been identified to substitute the reprogramming factors for iPSC generation as well as for direct differentiation of somatic cells into CMs without an intermediary pluripotent state. This review provides a concise update on the generation of iPSC-derived CMs and their application in personalized cardiac regenerative medicine. It also discusses the current limitations and challenges in the application of iPSC-derived CMs. Keywords Cardiomyocytes . Cardiac tissue engineering . Direct reprogramming . Pluripotent stem cells . iPSC . Regenerative medicine
Introduction Induced pluripotent stem cells (iPSCs) are laboratory-derived stem cells that can be reprogrammed from somatic cells by introducing reprogramming factors using viral or non-viral vectors. Colonies of iPSCs morphologically, molecularly and phenotypically resemble embryonic stem cells (ESCs).
* Joaquim M. S. Cabral [email protected] * Mukesh Kumar Gupta [email protected] 1
Department of Biotechnology, Institute of Engineering and Technology (IET), Bundelkhand University, Jhansi, Uttar Pradesh 284128, India
2
Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha 769 008, India
3
Department of Bioengineering, and iBB – Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
They possess self-renewal and pluripotency properties to differentiate into cells of all three germ layers [1–3]. Therefore, they are considered a valuable tool for in vivo and in vitro study of human development and related diseases. It additionally provides an advantage of being patient-specific autologo
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