Myocardial Reprogramming Medicine: The Development, Application, and Challenge of Induced Pluripotent Stem Cells

Abstract

Induced pluripotent stem cells (iPSCs) can be generated by reprogramming of adult/somatic cells. The somatic cell reprogramming technology offers a promising strategy for patient-specific cardiac regenerative medicine, disease modeling, and drug discovery. iPSCs are an ideal potential option for an autologous cell source, as compared to other stem/progenitor cells, because they can be propagated indefinitely and are able to generate a large number of functional cardiovascular cells. However, there are concerns about the specificity, efficiency, immunogenicity, and safety of iPSCs which are major challenges in current translational studies. In order to bring iPSC technology closer to clinical use, fundamental changes in this technique are required to ensure that therapeutic progenies are functional and nontumorigenic. It is therefore critical to understand and investigate the biology, genetic, and epigenetic mechanisms of iPSCs generation and differentiation. In this spotlight paper the discovery, history, and relative mechanisms of iPSC generation are summarized. The current technological improvements and potential applications are highlighted along with the important challenges and perspectives. Finally, emerging technologies are presented in which improvements to iPSC generation and differentiation approaches might warrant further investigation, such as integration-free approaches, direct reprogramming, and the development of iPSC banking.

Mir-195: Roadblock for Reprogramming Aged Cells

“…Currently available somatic cell reprogramming technologies offer a promising strategy for patient-specific cardiac regenerative medicine, disease modelling, and drug discovery [2]. Induced pluripotent stem cells (iPSCs) are an ideal potential option as an autologous cell source (as compared to other stem/progenitor cells) because they can be propagated indefinitely and large number of functional target cells can be generated [3].…”

Activation of MG53 Enhances Cell Survival and Engraftment of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Injured Hearts

“…The most common route of cell delivery for myocardial therapy involves intravenous, cell sheet, or direct intramyocardial injection into infarcted hearts [ 2 ]. One alternative treatment that has shown promise in preclinical studies is the use of human induced pluripotent stem cells (HiPSCs) for infarcted myocardial repair [ 3 ]. HiPSCs can be expanded indefinitely in culture, producing a potentially unlimited source of differentiated cells including cardiomyocytes (CM) for therapeutic applications [ 4 , 5 ].…”

“…HiPSC-derived CMs (HiPSC-CMs) have several potential advantages for the treatment of MI, such as being generated from a patient's own cells, allowing for a personalized treatment approach that minimizes the risk of immune rejection and reduces the need for immunosuppressive drugs [ 6 ]. Importantly, the risk of tumorigenicity of pluripotent stem cells can be avoided by morphological selection, labelling, or staining strategies using fluorescence activated cell sorters (FACS), or drug selection approaches [ 3 , 7 ]. Remarkably, HiPSC-CMs can be produced consistently and reproducibly using a chemical method based on the marked glucose/lactate metabolism characteristics of CMs, with purity reaching up to 99% and avoiding tumor formation after transplantation [ 8 ], ensuring a standardized and reliable product for use in therapy.…”