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.

Human Induced Pluripotent Stem Cell-Derived Exosomes as a New Therapeutic Strategy for Various Diseases

“…The mutated genes of diseased iPSCs can be repaired using the homologous recombination method and differentiated into therapeutic somatic cells and then sequentially transferred into diseased patients for cell therapy. In addition, iPSCs generated from healthy or diseased cells can also be used for the in vitro screening of drug candidates [ 3 , 4 , 5 , 6 , 7 , 8 ]. In consideration of the possibility of eliciting alloimmune responses towards allogeneic iPSCs, autologous iPSC-differentiated therapeutic cells are preferred for use in diseased patients.…”

iPSC Preparation and Epigenetic Memory: Does the Tissue Origin Matter?

“…Recently, iPSCs have been produced by choosing less invasive cells to obtain, such as keratinocytes isolated from hair follicles [74]. Very often, cell sources have been obtained from biological waste material [75]. Examples include renal epithelial cells in the urine [27,76], mesenchymal stem cells from teeth and fat tissue [77], liver and stomach cells [78], melanocytes [79], neural stem and progenitor cells [80], and embryonic and extraembryonic tissue [81].…”

Human Embryo Models and Drug Discovery

“…Their tri-lineage differentiation potential together with their non-transformed status are obvious advantages of hPSCs over conventional immortalized human cell culture models. These inherent characteristics of hPSCs including the fact that stem cells are perfectly amenable to genetic modifications [ 34 , 35 ] make them a powerful tool for both, studies on the molecular basis of human diseases and hPDD [ 4 , 31 , 36 , 37 , 38 ]. On the other hand, as for most other cell types, traditional 2D cultivation of hPSCs and their differentiated derivatives exhibits inevitable technological limitations and conceptual biases.…”