Cellular reprogramming for understanding and treating human disease

Abstract

In the last two decades we have witnessed a paradigm shift in our understanding of cells so radical that it has rewritten the rules of biology. The study of cellular reprogramming has gone from little more than a hypothesis, to applied bioengineering, with the creation of a variety of important cell types. By way of metaphor, we can compare the discovery of reprogramming with the archeological discovery of the Rosetta stone. This stone slab made possible the initial decipherment of Egyptian hieroglyphics because it allowed us to see this language in a way that was previously impossible. We propose that cellular reprogramming will have an equally profound impact on understanding and curing human disease, because it allows us to perceive and study molecular biological processes such as differentiation, epigenetics, and chromatin in ways that were likewise previously impossible. Stem cells could be called “cellular Rosetta stones” because they allow also us to perceive the connections between development, disease, cancer, aging, and regeneration in novel ways. Here we present a comprehensive historical review of stem cells and cellular reprogramming, and illustrate the developing synergy between many previously unconnected fields. We show how stem cells can be used to create in vitro models of human disease and provide examples of how reprogramming is being used to study and treat such diverse diseases as cancer, aging, and accelerated aging syndromes, infectious diseases such as AIDS, and epigenetic diseases such as polycystic ovary syndrome. While the technology of reprogramming is being developed and refined there have also been significant ongoing developments in other complementary technologies such as gene editing, progenitor cell production, and tissue engineering. These technologies are the foundations of what is becoming a fully-functional field of regenerative medicine and are converging to a point that will allow us to treat almost any disease.

Cell Reversal From a Differentiated to a Stem-Like State at Cancer Initiation

“…This is executed in such a way that the cell survives and performs its duty in the appropriate fashion for the human being continuity and development. Each particular differentiated cell type corresponds to a distinct epigenetic state, specified by, for instance, DNA methylation and histone modification (8,9), which depends on the tissue where it is placed (its microenvironment) and the development stage of the individual (the particular moment in its maturation history).…”

miR‐16 enhances miR‐302/367‐induced reprogramming and tumor suppression in breast cancer cells

“…Some landmark studies demonstrated that the cell fate could also be manipulated by combinations of some transcription factors such as OCT3/4, SOX2, KLF4, and MYC (OSKM) or OCT3/4, SOX2, NANOG, and LIN28 (OSNL), which induce somatic cell reprogramming and generate induced pluripotent stem cells (iPSCs) . Cellular reprogramming primarily happens through affecting signaling networks, which control the epigenetic state of the cell …”

“…4,5 Cellular reprogramming primarily happens through affecting signaling networks, which control the epigenetic state of the cell. 6 miRNAs constitute a class of 17-24 bp small noncoding RNAs which primarily bind to the 3 0 -untranslated region (UTR) and regulate gene expression. 7 miRNAs play an important role in regulation of different biological processes and malignant features of cancer cells such as apoptosis, proliferation, invasion, migration, stemness, and chemoresistance.…”

RNAi-Based Techniques for the Analysis of Gene Function in Drosophila Germline Stem Cells

“…Stem cells in the developing embryo and in some adult tissues allow for the continuous production of cells that can be instructed to differentiate into a variety of specialized fates. This unique ability, combined with recent advances in cell reprogramming and gene editing, has heightened clinical interest in the properties of stem cells [2]. Safe and effective use of stem cells and their progeny in regenerative therapies will require a detailed knowledge of the molecular factors that regulate stem cell function.…”