Abstract

Recent progresses in the field of Induced Pluripotent Stem Cells (iPSCs) have opened up many gateways for the research in therapeutics. iPSCs are the cells which are reprogrammed from somatic cells using different transcription factors. iPSCs possess unique properties of self renewal and differentiation to many types of cell lineage. Hence could replace the use of embryonic stem cells (ESC), and may overcome the various ethical issues regarding the use of embryos in research and clinics. Overwhelming responses prompted worldwide by a large number of researchers about the use of iPSCs evoked a large number of peple to establish more authentic methods for iPSC generation. This would require understanding the underlying mechanism in a detailed manner. There have been a large number of reports showing potential role of different molecules as putative regulators of iPSC generating methods. The molecular mechanisms that play role in reprogramming to generate iPSCs from different types of somatic cell sources involves a plethora of molecules including miRNAs, DNA modifying agents (viz. DNA methyl transferases), NANOG, etc. While promising a number of important roles in various clinical/research studies, iPSCs could also be of great use in studying molecular mechanism of many diseases. There are various diseases that have been modeled by uing iPSCs for better understanding of their etiology which maybe further utilized for developing putative treatments for these diseases. In addition, iPSCs are used for the production of patient-specific cells which can be transplanted to the site of injury or the site of tissue degeneration due to various disease conditions. The use of iPSCs may eliminate the chances of immune rejection as patient specific cells may be used for transplantation in various engraftment processes. Moreover, iPSC technology has been employed in various diseases for disease modeling and gene therapy. The technique offers benefits over other similar techniques such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. Thus, the applications of iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner.

Highlights

  • Discovery of self-renewal by any living cell was one of the major breakthrough reported by Till and McCulloch (1961) who while subjecting the mice with lethal doses of radiation followed by injection of bone marrow cells found that these cells formed clumps due to cells cloned from them which was the main reason of survival of the mice (Till and McCulloch, 1961)

  • Further research conducted on human stem cells (HSCs) made burgeoning use of human Embryonic Stem Cells (ESC) for which embryo needed to be isolated on regular basis that evoked several ethical issues among socio-research communities

  • The major breakthrough came in 2006 when Takahashi and Yamanaka introduced the concept of induced pluripotent stem cells by generating stem cells that were having properties relating to ESCs. iPSCs were generated by using a combination of 4 reprogramming factors, including Oct4 (Octamer binding transcription factor-4), Sox2 (Sex determining region Y)-box 2, Klf4 (Kruppel Like Factor-4), and c-Myc and were demonstrated both self-renewing and differentiating like ESCs, and could be used as an alternative for hESCs in various clinics/research

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Summary

INTRODUCTION

Discovery of self-renewal by any living cell was one of the major breakthrough reported by Till and McCulloch (1961) who while subjecting the mice with lethal doses of radiation followed by injection of bone marrow cells found that these cells formed clumps due to cells cloned from them which was the main reason of survival of the mice (Till and McCulloch, 1961). The major breakthrough came in 2006 when Takahashi and Yamanaka introduced the concept of induced pluripotent stem cells (iPSCs) by generating stem cells that were having properties relating to ESCs. iPSCs were generated by using a combination of 4 reprogramming factors, including Oct (Octamer binding transcription factor-4), Sox (Sex determining region Y)-box 2, Klf (Kruppel Like Factor-4), and c-Myc and were demonstrated both self-renewing and differentiating like ESCs, and could be used as an alternative for hESCs in various clinics/research. The various sources, delivery methods and their cognate approaches with different combinations of transcription factors differ significantly in their efficiency (Tables 2, 3) Since their discovery, iPSCs have been used in many research and clinical studies including disease modeling, regenerative medicine, and drug discovery/drug cytotoxicity studies. Frontiers in Cell and Developmental Biology | Stem Cell Research iPSCs and their clinical applications

Integrating methods
Nonintegrating methods
LIMITATIONS
Findings
CONCLUSION
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