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

Yigang Wang

doi:10.1155/2014/756240

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.

Highlights

Myocardial infarction (MI) is an important manifestation of coronary artery disease (CAD) and major cause of death and disability worldwide
somatic cell nuclear transfer (SCNT) studies demonstrated that differentiated cells or somatic cells retain all of the genetic information in nuclei as early embryonic cells, which are required for the entire organism development
Cell surface markers can be used to identify and isolate the cardiac cardiovascular progenitor population derived from Induced pluripotent stem cells (iPSCs), and their transplantation has demonstrated a robust ability for engraftment and differentiation into morphologically and electrophysiologically mature adult cardiomyocytes [267]

Summary

Introduction

Myocardial infarction (MI) is an important manifestation of coronary artery disease (CAD) and major cause of death and disability worldwide. SCNT studies demonstrated that differentiated cells or somatic cells retain all of the genetic information in nuclei as early embryonic cells, which are required for the entire organism development In these trials, the nucleus of oocyte was exchanged with the genome of a somatic cell using SCNT technology to generate pluripotent stem cells for regenerative applications [20]. Stem cell lines derived from these artificial blastocysts were capable of differentiation into cell types of all three germ layers This reprogramming approach requires private egg donation from women and the support of ethical policies [21]. The iPSC technology using adult somatic cells avoids the ethical issues raised in ESCs. In addition, the differentiation of iPSCs into functional cells is beneficial for cell based therapy and plays an important role in the establishment of patient-specific disease models for drug discovery and development. Integration-free methods: -Nonintegrating virus -Plasmids -Recombinant proteins -Synthesized mRNA -MicroRNAs -Small molecules iPSCs

Generation of iPSCs

Gene Transduction

The Potential Application of Somatic Cell Programming Strategy

Challenges and Perspectives of iPSCs

Findings

Summary