Krüppel-like factor 4 (KLF4) is an oncogene that contributes to the long-term maintenance of the ESC phenotype. The c-MYC protein can also induce global histone acetylation allowing OCT4 and SOX2 to bind to otherwise inaccessible sites. The proto-oncogene c-MYC has multiple downstream targets that enhance cell proliferation, resulting in SC self-renewal. It comprises a regulatory complex with OCT4 and REX1 that cooperatively binds to DNA to activate transcription of other pluripotency factors. The transcription factor SOX2 (sex determining region Y (SRY)-box2) is also essential for maintaining cell pluripotency. The level of OCT4 expression is vital for regulating pluripotency and it can both activate or repress the promoter of the REX1 gene, also a critical regulator of pluripotency. OCT4 is a key transcriptional factor, which maintains pluripotency in both early embryos and ESCs. Oct4, Sox2, c-Myc, and Klf4 were later identified by Takahashi and Yamanaka as sufficient to induce pluripotency in mouse somatic cells, resulting in iPSCs that were functionally equivalent to mouse ESCs. The success of animal cloning has demonstrated that unfertilized eggs and ESCs contain a set of factors that can confer pluripotency to somatic cells. This chapter discusses the current progress and prospects of using the iPSC technology in tissue replacement therapy and as a tool for studying human pathologies. However, despite the tremendous potential of iPSCs, extensive analyses of their safety and reliability are still required. Significant advances have been achieved in recent years in improving the safety of the iPSC technology thus, expanding the opportunities for its clinical application. Thus, the iPSC technology solves many problems associated with the use of ESCs and provides an unlimited source of autologous pluripotent SCs, which can be genetically corrected, differentiated into adult lineages, and returned to the same patient as an autograft. Similar to ESCs, iPSCs can proliferate indefinitely and differentiate into all three germ layers. ESC-based cell therapies may also result in immune rejection, which theoretically can be avoided if autologous iPSC-derived cells are used instead. Primary human ESCs, therefore, are a suboptimal SC source for therapy and tissue engineering. Additionally, the use of ESCs is obstructed by the need to destroy human embryos in the process of cell isolation, which raises ethical considerations. Therefore, unlike the iPSC technology, ESC-based techniques do not allow for the generation of genetically diverse patient-specific cells. Human ESCs are isolated by the use of surplus in vitro fertilization embryos. iPSCs share many similarities with ECSs, including pluripotency, differentiation potential, and the capability to form teratomas and viable chimeras. Adult SCs are multipotent cells of adult tissues that are also essential for regenerative medicine. They can give rise to tissues of the three germ layers and are regarded as a renewable potent cell source for the regeneration of all bodily tissues. ESCs are pluripotent cells derived from the inner cell mass of the blastocyst. Based on their origin, SCs are divided into embryonic SCs (ESCs), induced pluripotent SCs (iPSCs), and adult SCs. Stem cells (SCs) have the ability to self-renew through cell division and can differentiate into various cell types. Human iPSCs represent an unprecedented source of patient-specific pluripotent stem cells suitable for disease modeling and tissue replacement therapy. Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) through the ectopic expression of reprogramming factors has had a dramatic impact on the field of regenerative medicine and has opened a new era in research and therapy.
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