Preclinical studies for induced pluripotent stem cell-based therapeutics

Abstract

Induced pluripotent stem cells (iPSCs) and their differentiated derivatives can potentially be applied to cell-based therapy for human diseases. The properties of iPSCs are being studied intensively both to understand the basic biology of pluripotency and cellular differentiation and to solve problems associated with therapeutic applications. Examples of specific preclinical applications summarized briefly in this minireview include the use of iPSCs to treat diseases of the liver, nervous system, eye, and heart and metabolic conditions such as diabetes. Early stage studies illustrate the potential of iPSC-derived cells and have identified several challenges that must be addressed before moving to clinical trials. These include rigorous quality control and efficient production of required cell populations, improvement of cell survival and engraftment, and development of technologies to monitor transplanted cell behavior for extended periods of time. Problems related to immune rejection, genetic instability, and tumorigenicity must be solved. Testing the efficacy of iPSC-based therapies requires further improvement of animal models precisely recapitulating human disease conditions.

Keywords: Animal Models; Differentiation; Induced Pluripotent Stem Cell (iPSC); Regenerative Medicine; Stem Cells.

FIGURE 1.

Overview of the workflow for development and preclinical testing of iPSC-based therapeutics. The application of iPSC-derived products for therapy raises a number of issues that should be addressed to ensure safe and efficient treatment of human disease conditions. These challenges relate to the unique properties of the cells and will require development of novel technologies as well as assessment of additional risk factors, which are not addressed using current procedures for preclinical testing of biopharmaceuticals.