Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development

Abstract

The discovery of somatic cell nuclear transfer proved that somatic cells can carry the same genetic code as the zygote, and that activating parts of this code are sufficient to reprogram the cell to an early developmental state. The discovery of induced pluripotent stem cells (iPSCs) nearly half a century later provided a molecular mechanism for the reprogramming. The initial creation of iPSCs was accomplished by the ectopic expression of four specific genes (OCT4, KLF4, SOX2, and c-Myc; OSKM). iPSCs have since been acquired from a wide range of cell types and a wide range of species, suggesting a universal molecular mechanism. Furthermore, cells have been reprogrammed to iPSCs using a myriad of methods, although OSKM remains the gold standard. The sources for iPSCs are abundant compared with those for other pluripotent stem cells; thus the use of iPSCs to model the development of tissues, organs, and other systems of the body is increasing. iPSCs also, through the reprogramming of patient samples, are being used to model diseases. Moreover, in the 10 years since the first report, human iPSCs are already the basis for new cell therapies and drug discovery that have reached clinical application. In this review, we examine the generation of iPSCs and their application to disease and development.

Advances on Bone Substitutes through 3D Bioprinting

“…However, adult stem cells are scattered throughout tissues and their expansion is impaired or limited by their proliferative ability. To overcome these limitations, a solution is represented by induced pluripotent stem cells (iPSCs), which have been tested in many well-reviewed studies [ 110 , 111 ]. IPSCs can be produced from different cell types, but most often from fibroblasts.…”

Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: A pluripotent stem cell-based approach

“…These induced pluripotent stem cells (iPSCs) possess almost the same features as ESCs and represent an incredibly promising source of autologous cells for transplantation purposes. Following this original discovery, numerous studies reported the ability of different somatic cell types (such as keratinocytes or blood cells) to be reprogrammed and the development of non-integrative delivery methods (such as episomal plasmids or RNA) for reprogramming (González et al, 2011;Karagiannis et al, 2019).…”

Characterization of iPS87, a prostate cancer stem cell-like cell line

“…Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem (ES) cells, and their over-expression has been shown to induce pluripotency and immortalization in both mouse and human somatic cells. These factors regulate the signaling network necessary for ES cell pluripotency and, typically, human iPSCs express stem cell markers and are capable of producing differentiated cells characteristic of all three germ layers [4][5][6]. In the work described here, we employed this approach towards a slightly different goal: to immortalize and restore tumorigenic properties to human PCSC.…”