Human induced pluripotent stem cells for monogenic disease modelling and therapy

Abstract

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: Differentiation; Foetal cells; Gene editing; Gene therapy; Human induced pluripotent stem cells; Monogenic diseases; Reprogramming techniques.

Figure 1

Representation of the workflow for the derivation of patient-specific induced stem cells from foetal or somatic cells and successively their use for the development of personalized therapy protocols. CVS: Chorionic villus sampling; AF: Amniotic fluid; hiPSCs: Human induced pluripotent stem cells.