Chapter 8 - Applications of iPSCs in Gaucher Disease and other rare sphingolipidoses

Abstract

In this chapter, an overview of various applications of induced pluripotent cells (iPSCs) is given. This chapter focuses on the uses of iPSCs in inherited diseases and, particularly, in the case of Gaucher disease (GD). This disease is one of the most common sphingolipidoses, a subgroup of lysosomal storage disorders (LSDs), and was the first LSD to be used in the generation of iPSCs. Several models have been developed with multiple GD donors, recapitulating the phenotypic hallmarks of the disease. These models have provided a new platform for pathophysiology studies and for the testing of small molecules with therapeutic goals. Furthermore, the use of iPSCs as a source of differentiated cells together, with specific culturing conditions, has provided encouraging results regarding the regeneration of systems that suffer degeneration in GD and in other LSDs. Therefore, the use of iPSCs and differentiated disease target cells is foreseen as a sustainable approach for the regeneration of various organs and systems. Clinical therapeutical strategies, based on the use of autologous iPSC-derived cells to treat patients, can be particularly promising when combining the use of iPSCs techniques with other emerging techniques such as gene editing, RNA therapeutics and nanomaterials. The fast technical advances in the various fields of molecular and cell biology, some of which were boosted during the pandemic, are expected to provide a myriad of possibilities for the development of new therapeutic cell-based approaches and assays.