Disease-specific Induced Pluripotent Stem Cells

Although in vitro cell culture is a cornerstone of normal and pathological biomedical research, it has always been limited by the presence of artifacts, genetic and otherwise, and the requirement of using either primary or genetically modified cells to allow immortal propagation. In contrast, human embryonic stem cells, which are pluripotent and theoretically able to form any cell type, can establish more accessible models of human disease and are capable of differentiating into a variety of tissue types in various disease states. In a recent article, “Disease-specific Induced Pluripotent Stem Cells,” the authors reprogrammed cells from patients with a number of different diseases, including Parkinson's disease and Huntington's disease, to form pluripotent stem cells that were capable of differentiating into any tissue type (Cell 134:877–886, 2008). These techniques present unique opportunities to better understand the development of central nervous system diseases. The cells derived from these methods can also be used to test therapeutics, or used as therapeutics themselves in cell replacement treatments.

Viral vectors carrying transcription factors were introduced into dermal fibroblasts or bone marrow-derived mesenchymal cells obtained from patients with a prior disease diagnosis and were cultured to form embryonic stem cell-like colonies. These induced pluripotent stem cells underwent genetic characterization and karyotype analysis to confirm that they represented the parental cell disease state. Through immunohistochemistry, gene expression analysis, and differentiation and teratoma formation studies, the authors were also able to prove that the cells were, in fact, stem cells. Ultimately, the authors successfully formed stem cells with Huntington-defining CAG polyglutamine repeats as well as stem cells to model Parkinson's disease, which has a more complex genetic predisposition.

Induced stem cell disease modeling, neurological or otherwise, offers an invaluable opportunity to more accurately represent in vivo disease through in vitro cell culture. In the neurodegenerative diseases studied (Huntington's disease and Parkinson's disease), genetically defined stem cells can contribute significantly to data already gathered from animal models and differentiation studies. This work can be expanded to study countless other neurological diseases. Induced disease-specific stem cells can revolutionize cell culture-based research and help bridge the gap between bench research and the bedside.