Since their discovery in 2006 by Japanese researcher Shinya Yamanaka of Kyoto University, induced Pluripotent Stem cells (iPSCs) have attracted worldwide attention, especially in the field of regenerative medicine (STEM CELL SCHOOL, 2011). It was first thought that as a cell proceeds along its specialised cell lineage, it would not have the ability to reprogram itself to a pluripotent state (STEM CELL SCHOOL, 2011). Since the birth of Dolly the sheep in 1996, which proved to the world that somatic cells can in fact be reverted to an embryonic state to develop into an organism, through a cloning technique known as somatic cell nuclear transfer (SCNT), researchers have been exploring possible regenerative processes to reprogram a somatic cell into an iPSC (STEM CELL SCHOOL, 2011).
Pluripotent stem cells, found in early developmental stages of embryos, are cells that are able to differentiate into specialised cell lineages to form various organs and tissues that make up an organism’s body (Reece, J et al. 2011). It can be said that stem cells are the biological, developmental basis of all multicellular organisms. There are four types of stem cells. These include adult, fetal, embryonic and induced stem cells (Bedford Stem Cell Research Foundation, 2009).
iPSCs were first produced in the laboratory in 2006 by Shinya Yamanaka while experimenting on fibroblasts from mice (Center for iPS Cell Research and Application – iPS Basics, 2009). Yamanaka’s team discovered only four of the 24 genes tested would be needed to reprogram the mice fibroblast cells into pluripotent stem cells, these genes were Oct-4, SOX2, Klf-4 and c-Myc (STEM CELL SCHOOL, 2011). The Oct-4 and SOX2 genes were to maintain and regulate pluripotency characteristics (STEM CELL SCHOOL, 2011). c-Myc was introduced for its function to maintain cell growth, differentiation, cell death and has shown to increase the efficiency of reverting cells to iPSCs, however it is linked to the formation of cancer (STEM CELL SCHOOL, 2011). Klf-4 aids in cell differentiation and survival, and is greatly expressed in embryonic stem cells (STEM CELL SCHOOL, 2011).
In developed somatic cells, such as skin cells, the genes for pluripotency are in fact present, though they are repressed or inactive. To achieve pluripotency characteristics, Yamanaka and his team introduced the genes into cells via a retrovirus vector, thereby overexpressing the genes (Center for iPS Cell Research and Application – iPS Basics, 2009). The process by which genes are introduced into a host cell via a virus vector is known as transfection. To incorporate the four genes into the DNA of a somatic cell, the genes are spliced into the retrovirus which then infects the host cell (Center for iPS Cell Research and Application – iPS Basics, 2009). Using this RNA virus presents a different set of health and safety problems. Retroviruses allow the genes to integrate and persist to be active in the host cell; however as a consequence the retrovirus itself integrates as part of the host cell’s genome, leading to the DNA to be damaged and the possibility for the cell to become cancerous (Hochendlinger, K 2010). To over come this problem, current methods involve other RNA viruses such as adenoviruses, lentiviruses, micro-RNAs & bacterial plasmids.
As iPSCs have the potential to be used for a number of applications, further research into their production should overcome much of the ethics surrounding stems cells. iPSCs are able to be used for drug models, studying diseases and used for organ or tissue transplants, that can be made from a patient’s own cells, reducing immune rejection (Hadenfeld, M 2010).
iPSCs have enormous potential to be utilized in the medical field. They are produced by introducing four specific genes into a somatic cell, via a retrovirus vector, which leads to the cell to reprogram itself. Due to some health and safety issues of this procedure, safer ways of incorporating the genes are being investigated. iPSCs have revolutionized regenerative medicine and would prove to be of great benefit in the future.
Bedford Stem Cell Research Foundation, 2009, viewed 20 March 2012, <http://www.bedfordresearch.org/stemcell/stemcell.php?item=what-is-a-stem-cell>
Center for iPS Cell Research and Application – iPS Basics, 2009, viewed 19 March 2012, <http://www.cira.kyoto-u.ac.jp/e/faq/faq2.html>
Hadenfeld, M 2010, Reprogramming: how to turn any cell of the body into a Pluripotent stem cell, viewed 19 March 2012, <http://www.eurostemcell.org/factsheet/reprogramming>
Hochendlinger, K 2010, Your Inner Healers: A Look into the Potential of Induced Pluripotent Stem Cells, viewed 19 March 2012, <http://www.scientificamerican.com/article.cfm?id=your-inner-healers>
Reece, J et al. 2011, Cambell BIOLOGY Ninth Edition Australian Version, PEARSON, Sydney
STEM CELL SCHOOL, 2011, viewed 19 March 2012, <http://www.stemcellschool.org/>, <http://www.stemcellschool.org/ig-stem-cell.html>