Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2016; 8(4): 118-135
Published online Apr 26, 2016. doi: 10.4252/wjsc.v8.i4.118
Human induced pluripotent stem cells for monogenic disease modelling and therapy
Paola Spitalieri, Valentina Rosa Talarico, Michela Murdocca, Giuseppe Novelli, Federica Sangiuolo
Paola Spitalieri, Valentina Rosa Talarico, Michela Murdocca, Giuseppe Novelli, Federica Sangiuolo, Department of Biomedicine and Prevention, Tor Vergata University, 00133 Rome, Italy
Author contributions: Spitalieri P and Sangiuolo F contributed to drafting and making critical revisions of the article; Talarico VR and Murdocca M contributed to analysis and interpretation of data; Novelli G contributed to final approval of the version of the article to be published.
Supported by Agenzia Spaziale Italiana (ASI), CoReA, No. 2013-084-R.0.
Conflict-of-interest statement: The authors declare no conflicts of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Federica Sangiuolo, PhD, Department of Biomedicine and Prevention, Tor Vergata University, via Montpellier, 1, 00133 Rome, Italy.
Telephone: +39-06-72596164 Fax: +39-06-20427313
Received: September 9, 2015
Peer-review started: September 10, 2015
First decision: October 8, 2015
Revised: January 21, 2016
Accepted: February 14, 2016
Article in press: February 16, 2016
Published online: April 26, 2016

Recent and advanced protocols are now available to derive human induced pluripotent stem cells (hiPSCs) from patients affected by genetic diseases. No curative treatments are available for many of these diseases; thus, hiPSCs represent a major impact on patient’ health. hiPSCs represent a valid model for the in vitro study of monogenic diseases, together with a better comprehension of the pathogenic mechanisms of the pathology, for both cell and gene therapy protocol applications. Moreover, these pluripotent cells represent a good opportunity to test innovative pharmacological treatments focused on evaluating the efficacy and toxicity of novel drugs. Today, innovative gene therapy protocols, especially gene editing-based, are being developed, allowing the use of these cells not only as in vitro disease models but also as an unlimited source of cells useful for tissue regeneration and regenerative medicine, eluding ethical and immune rejection problems. In this review, we will provide an up-to-date of modelling monogenic disease by using hiPSCs and the ultimate applications of these in vitro models for cell therapy. We consider and summarize some peculiar aspects such as the type of parental cells used for reprogramming, the methods currently used to induce the transcription of the reprogramming factors, and the type of iPSC-derived differentiated cells, relating them to the genetic basis of diseases and to their inheritance model.

Keywords: Human induced pluripotent stem cells, Gene therapy, Monogenic diseases, Gene editing, Foetal cells, Reprogramming techniques, Differentiation

Core tip: With the development of human induced pluripotent stem cells (hiPSCs) deriving from patients, we can begin to understand the molecular mechanisms underlying monogenic diseases and consequently identify new drugs for their treatment. hiPSCs can differentiate into many disease-relevant cell types, providing in this way to innovative applications in the field of cell replacement therapy, disease modelling, drug testing and drug discovery.