Reprogramming somatic cells to induced pluripotent stem cells (iPSC): A cellular career change
Grant Agreement No. 951890
EU Partners from a wide range of locations have come together to deliver the Platforma project; HANNOVER (DE), GARBSEN (DE), BIRMINGHAM, CAMBRIDGE, EDINBURGH (UK), GEMBLOUX (BE) – December 2020
The consortium has received a prestigious project worth 2.0 million euros from the European Commission as part of the EIC Pathfinder program “EIC Transition to Innovation” and European partners.
PLATFORMA, the name of the European consortium, wants to develop and manufacture novel 3D cell platforms for the screening of cosmetics, pollutants and new therapeutics. This means that examinations can be simulated directly on human tissue in order to make animal experiments in these areas superfluous in the future.
In the UK region, Axol Bioscience plays a significant role in utilizing their expert knowledge in both IPSC cell types for the Peripheral nervous system cell types, i.e. Sensory neurons and Motor neurons and Multi-Electrode array, to deliver biologically relevant 3D cell models.
Somatic cells can be compared to human beings in that they grow up to perform a specific function in life. While a human being may develop into a world class athlete or a research scientist, a somatic cell can develop into any of the cell types that make up an organism except the germline cells.
Human beings and somatic cells are extremely fortunate to have so much choice available when it comes to deciding on a path, but what happens if we get bored of our chosen career? Although human beings have the option to re-train in a different profession, somatic cells require a little help from the experts to guide them smoothly into their next role.
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How to reprogram cells into iPSCs
A career change for a somatic cell is more accurately referred to as reprogramming and involves conversion of the cell to an induced pluripotent stem cell (iPSC) before differentiation into one of many diverse cell types.
Reprogramming can be achieved by using vectors to integrate DNA into the cell’s genome. This method has been shown to have success, but has its drawbacks. Potential issues include insertional mutagenesis and residual expression of reprogramming factors in cellular progeny. Integrating vectors hold little clinical appeal as their use does not preserve the original genomic integrity of the somatic cell.
The need to increase the therapeutic potential of iPSC has been one of the main drivers behind the development of non-integrating vectors. Many different strategies are under investigation, and currently the three most widely used non-integrating reprogramming systems are episomal vectors, Sendai virus vectors or mRNA transfection technology.
Episomal vector reprogramming uses components of the Epstein-Barr virus to facilitate delivery of reprogramming factors into somatic cells. This method is highly successful in generating iPSCs from peripheral blood mononuclear cells (PBMCs) and fibroblasts. It also enables a rapid loss of reprogramming vectors from the cells and is non-viral so does not require a category II tissue culture laboratory. We use a licenced four-factor episomal vector reprogramming method from iPS Academia, allowing us to provide reprogrammed cell lines to our customers that they can use to advance their research endeavors.
Sendai virus is non-pathogenic to humans and is incapable of integration into the host cell genome. The success rate of Sendai virus vector reprogramming in PBMCs and fibroblasts is high. The technology is associated with low aneuploidy and, although slower, has been found to be a more efficient method than episomal vector reprogramming in generating iPSCs. We license the CytoTune®-iPS 2.0 Sendai virus technology from ID Pharma and offer customers who do not have their own license the opportunity to access a project-specific sub-license as part of our cell reprogramming contract service .
mRNA transfection technology relies on the use of mRNA rather than DNA to deliver reprogramming factors to somatic cells. Although more efficient than the two non-integrating methods discussed previously, the procedure is less popular due to its complexity. Careful consideration must be given to the design of the mRNA to limit activation of an innate immune response to foreign nucleic acids. Repeat administration is also necessary since mRNA only has a short half-life.
Advancing research and development with reprogrammed iPSCs
Human beings have many reasons for wanting a career change, but why would a somatic cell choose to try something new? For somatic cells it doesn’t come down to choice and for this reason researchers should be thankful that the human body doesn’t contain a HR department organ for somatic cells to complain to.
Reprogramming of somatic cells is instead performed by highly specialised and skilled scientists who are motivated by the possibilities which patient-derived iPSCs hold for disease modeling, drug discovery, regenerative medicine and cell therapy. For example, although continuous cell lines have been used as a research tool by pharmaceutical companies for decades, iPSC-derived cells provide a more biologically relevant model of the in vivo system. They also hold huge potential in the generation of patient-specific iPSC- derived tissue grafts, which will dramatically reduce the risk of immune rejection and improve the patient’s quality of life.
The reprogramming of somatic cells into iPSCs holds great potential for the future, enabling scientists to push forward ground-breaking research and discover the next generation of therapeutics, why not discover how you can take advantage of this amazing opportunity.
Axol Bioscience is the place to go for all things iPSC-related. Not only do we produce a comprehensive range of iPSC-derived cells along with expertly optimised growth media for their successful culture and propagation, we also supply differentiated cells derived from healthy donors and patients of specific disease backgrounds. Our expertise includes reprogramming cells to iPSCs and differentiating them to various cell types, while within our custom service offerings we can take cells provided by you and carry out reprogramming and differentiation on your behalf, saving you both time and money.