Pluripotent Stem Cells
The ability of cells to differentiate into various cell types is known as "pluripotency"
(see figure).
In 2006, researchers at Kyoto University in Japan identified conditions that would allow specialized adult cells to be genetically "reprogrammed" to assume a stem cell-like state. These adult cells, called induced pluripotent stem cells (iPSCs), were reprogrammed to an embryonic stem cell-like state by introducing genes important for maintaining the essential properties of embryonic stem cells (ESCs). Since this initial discovery, researchers have rapidly improved the techniques to generate iPSCs, creating a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined.
Pluripotent stem cells and induced pluripotent stem cells (iPSCs) replicate in culture dishes and are theoretically capable of giving rise to any of the cell types found in the body. iPSCs are transforming the field of regenerative medicine. iPSCs can be generated by the transduction of four genes encoding transcription factors such as Oct3/4, Sox2, Klf4, and c-Myc. It was discovered that these four factors were sufficient to trigger the reprogramming of human somatic cells and thus help to generate cells closely resembling the embryonic stem cells (ESCs). iPSCs can be used as a reliable method of producing patient- specific somatic tissue lines via directed differentiation. iPSC technology is expected to provide innovative tools for drug development via high-throughput therapeutic/toxicity screening, using differentiated cells from patient-derived iPSCs.
Although much additional research is needed, investigators are beginning to focus on the potential utility of iPSCs as a tool for drug development, modeling of disease, and transplantation medicine. The idea that a patient's tissues could provide him/ her a copious, immune-matched supply of pluripotent cells has captured the imagination of researchers and clinicians worldwide. Furthermore, ethical issues associated with the production of ESCs do not apply to iPSCs, which offer a non-controversial strategy to generate patient-specific stem cell lines.
In our lab we are focusing on the generation of human iPSCs for various disease conditions/ various healthy individuals. These reprogrammed cells are used for the discovery of novel disease mechanisms and in the development of novel drug therapies and also for drug screening applications.
Figure 1: Human primary fibroblasts reprogrammed into human iPS cells using OCT4, Sox2, KLF4 and c-Myc sendai virus
Figure 2: Human iPS cells derived from fibroblasts display pluripotency cell surface marker (TRA-1-60) expression
