Reprogrammed cells for disease modeling and regenerative medicine

Abstract

The conversion of somatic cells into pluripotent cells is transforming the way diseases are researched and treated. Induced pluripotent stem (iPS) cells' promise may soon be realized in the field of hematology, as hematopoietic stem cell transplants are already commonplace in clinics around the world. We provide a current comparison between induced pluripotent and embryonic stem cells, describe progress toward modeling hematological disorders using iPS cells, and illustrate the hurdles that must be overcome before iPS cell therapies will be available in clinics.

Figure 1. Epigenetic memory of original cell type

iPS cell lines differ in their ability to differentiate towards various cell lineages. In many cases, iPS cell lines differentiate more robustly towards cell types related to the lineage from which they were reprogrammed than towards unrelated cell types (23, 24). This phenomenon is referred to as epigenetic memory.

Figure 2. Cellular therapy paradigm

This figure outlines the goals of stem cell-based regenerative medicine, first demonstrated in mouse by somatic cell nuclear transfer in 2002 (52) and iPS cell derivation in 2007 (53). The paradigm combines gene therapy and cellular therapy to provide a gene-corrected, autologous cell transplant to a patient.

Figure 3. Steps of disease modeling

I) Design and verify the disease model. Because of the large variability in behavior of pluripotent cell lines (23, 58, 59), disease models should be established using only genetically identical, disease-corrected controls. Robust protocols for differentiating iPS cells into the target tissues must be established, and a cellular phenotype must be identified that is both specific to the cells bearing the disease genotype and relevant to the disorder. II) Employ the disease model. Once a disease-specific cellular phenotype has been identified, the mechanism of the disease can be investigated. The model can also be assayed after experimental manipulations such as drug screens, in order to identify potential therapeutic agents.