Induced Pluripotency: A Powerful Tool for In Vitro Modeling

Abstract

One of the greatest breakthroughs of regenerative medicine in this century was the discovery of induced pluripotent stem cell (iPSC) technology in 2006 by Shinya Yamanaka. iPSCs originate from terminally differentiated somatic cells that have newly acquired the developmental capacity of self-renewal and differentiation into any cells of three germ layers. Before iPSCs can be used routinely in clinical practice, their efficacy and safety need to be rigorously tested; however, iPSCs have already become effective and fully-fledged tools for application under in vitro conditions. They are currently routinely used for disease modeling, preparation of difficult-to-access cell lines, monitoring of cellular mechanisms in micro- or macroscopic scales, drug testing and screening, genetic engineering, and many other applications. This review is a brief summary of the reprogramming process and subsequent differentiation and culture of reprogrammed cells into neural precursor cells (NPCs) in two-dimensional (2D) and three-dimensional (3D) conditions. NPCs can be used as biomedical models for neurodegenerative diseases (NDs), which are currently considered to be one of the major health problems in the human population.

Keywords: cell reprogramming; disease modeling; in vitro biomedical models; induced pluripotent stem cells; neural precursor cells; neurodegenerative disease.

Figure 1

(A,B)—Population of human dermal fibroblasts isolated from patient biopsy (blue, DAPI; cyan, phalloidin). (C)—Embryoid bodies formed in 3D cultivation conditions. (D,E)—iPSC colonies in 2D cultivation conditions. (F)—iPSC colonies grown on a layer of mouse embryonic fibroblasts (MEFs) (blue, DAPI; cyan, expressed transcription factor Nanog). Authors’ own images.

Figure 2

Small molecules for reprogramming and transdifferentiation that affect biochemical and molecular processes in cells. (PS48—Allosteric Phosphoinositide-Dependent Protein Kinase-1 (PDK1) agonist, VPA—Valproic Acid, TSA—Trichostatin A).

Figure 3

The most commonly used iPSC reprogramming approaches.

Figure 4

Use of the somatic cells of an adult patient through the stages of culturing, reprogramming, differentiation, biological characterization, in vitro modeling of disease, drug testing, and the possibility of their use in clinical practice and personalized regenerative medicine.