Clinical Applications of Human Induced Pluripotent: Challenges and Opportunities.

Abstract Human pluripotent stem cells can be derived from reprogrammed fibroblasts using overexpression of pluripotency factors (human induced pluripotent stem cells, or hIPSCs). These pluripotent cells are characterized by their capacity to self-renew in vitro while maintaining their property to differentiate into a broad number of cell types. By combining these unique properties, hIPSCs could enable the generation of large quantities of cells for clinical applications. Furthermore, the possibility of generating hIPSCs from somatic cells using epigenetic reprogramming represents a unique opportunity for regenerative medicine. Indeed, these pluripotent stem cells could enable the production of patient-specific cell types that are fully immuno-compatible with the original donor, thereby avoiding the need for immune suppressive treatment during cell-based therapy. hIPSCs can also be used to develop in vitro models of disease, allowing large-scale studies impossible with primary cell cultures or with biopsy material. This application has been proven useful to model neurodegenerative diseases, cardiac syndromes and inborn metabolic disorders in vitro for basic studies and drug screening. While these results demonstrate that hIPSCs could be useful to study a broad number of disease in vitro, key limitations have to be solved before these pluripotent stem cells become fully useful with clinical applications in vivo. Current approaches to reprogram cells are often associated with important issues such as genetic and epigenetic instability. Furthermore, protocols available to direct differentiation of hIPSCs lack the necessary efficiency and systematically result in the production of fetal derivatives. While such embryonic cells are mature enough to model some diseases in vitro, they might not be sufficiently functional for mimicking diseases affecting adult cells or for cell therapy applications. Therefore, further efforts are required to develop novel method to reprogram somatic cells and to generate fully mature cells from human pluripotent cells. Here, we will discuss the potential solutions necessary to generate hIPSCs compatible with cell therapy approaches against degenerative diseases especially genetic disorders affecting the liver.