Stem Cell Production
Induced Pluripotent Stem Cells (iPSC) are derived from differentiated, adult cells that have been coaxed to adopt a more embryonic stem cell-like state. Because the transcriptional network that controls pluripotency of human embryonic stem cells (hESC) has been studied extensively, it is now possible to express four of those transcription factors in adult cells, and reprogram them to have the characteristics of hESC; particularly self-renewal and pluripotency.
Induced pluripotent stem cells are being derived from patients carrying a number of diseases, and are particularly powerful in studying those that only affect humans, those with complex phenotypes, not associated with a particular cell type, or known gene. Ultimately, understanding and treating disease will require careful comparison of multiple cell lines carrying a full range of genetic abnormalities for a given disease, making iPSC particularly useful. In the longer term, because the cells are patient-derived, there is also the hope that they will be useful for transplantation without requiring immune suppression.
One field where iPSC are beginning to make an impact is in studying neurodegenerative conditions and neuroaffective disorders such as Bipolar Disorder (BP) and schizophrenia. Often referred to as, “brain in a dish”, these studies take advantage of the facts that these conditions originate early in life, many have high genetic risk, but there is often no identified neuropathology or clear genetic base. iPSC therefore provide an unsurpassed source of human neurons and glial cells, and a unique opportunity to identify common and novel pathways involved in abnormalities of gene expression, neuronal and glial differentiation, function and apoptosis characteristic of neurological and neuropsychiatric diseases.
Since the time of Pericles in classical Athens, scientists have puzzled over the causes of Bipolar Disorder. As its name suggests, individuals diagnosed with this condition cycle between periods of hyper-excitability and depression. Although the disorder affects more than 6 million Americans, surprisingly little is known about how it develops, and there is a critical, unmet need for new therapies. With support from the Prechter Fund in the Department of Psychiatry, researchers have derived a number of iPSC lines from donors with Bipolar Disorder, with the goal of understanding the progression of this devastating disorder and identifying more effective treatments for the millions of patients who suffer from BP worldwide.