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Induced pluripotent stem cell

Induced pluripotent stem cell

Induced Pluripotent Stem Cells, abbreviated as iPS cells or iPSCs, are generated in the laboratory by treating adult differentiated cells from sources such as skin, with factors that reprogram the cells to an undifferentiated pluripotent state. The cells can then be treated with factors that signal the cells to differentiate into another cell type.

iPS cells are useful for research and development of therapies because they are derived from accessible locations such as skin and blood and because they can be maintained in culture and expanded quickly.

Research into embryonic stem cells, the ability to create a clone of an organism by reprogramming the nucleus of an adult cell and the identification of master regulator genes that maintain cellular identity lead up to the ability to generate pluripotent stem cells from adult cells in the laboratory by supplying certain reprogramming factors. The first mouse iPS cells were generated using a retrovirus to introduce 4 transcription factors, c-Myc, Oct3/4, Sox2 and Klf4 into mouse skin fibroblasts by Shinya Yamanaka and his colleagues in 2006. Sox2 controls expression of Oct3/4. c-Myc recruits proteins that modify chromatin to cause widespread activation of gene transcription. c-Myc is also a proto-oncogene associated with causing various cancers. L-Myc can replace c-Myc and does not have the ability to transform cells into tumours.

Getting these factors into cells in order to reprogram them can be done a number of ways. Retroviruses and lentiviruses, used to deliver these iPS cell programming factors as transgenes, have a risk of causing mutations where they insert into the cell genome. The transgenes are silenced after reprogramming but carry the chance of reactivating which could potentially cause tumors. Adenovirus, plasmid vectors, removable piggyBac transposons and Sendai virus have been developed to deliver genes in transient way so they are not integrated into the genome. Certain chemical compounds such as valproic acid, sodium butyrate and histone deacetylase inhibitors have been shown to improve efficiency of iPS cell generation.

In March 2018 Sumitomo Dainippon Pharma opened the world’s first commercial iPS cell plant offering cells for commercial purposes. Their initial production of iPS cells will be for use in clinical trials. Production facilities for iPS cells that are available to researchers include the National Institutes of Health Center for Regenerative Medicine and the stem cell bank run by the WiCell Research Institute in Madison, Wisconsin, USA. The European Bank for induced pluripotent Stem Cells supplies iPS cell lines to researchers in academia and industry.

The two main applications from iPS cells are cell replacement therapy and drug discovery. An example of cell replacement therapy is to grow pancreas cells to transplant into patients with type I diabetes, where the immune system has destroyed the beta cells that produce insulin. For drug discovery research, iPS cells derived from patients with or without a certain disease can differentiated into cell and tissue types in order to model and understand the disease at the molecular level. These disease models can be used to identify drug targets and test potential therapies.

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Axol Bioscience

Celgene

Cellular Dynamics International

Censo Biotechnologies

Evotec

Horizon Discovery

iPS Academia Japan

Sanofi

Takeda

Thermo Fisher Scientific

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