The endless possibilities of iPSCs and organoids

On the 8th of October 2012, the Nobel Prize in Physiology was given to Shinya Yamanaka and John B. Gurdon for a groundbreaking discovery; induced Pluripotent Stem Cells (iPSCs). The two scientists discovered that mature, specialised cells can be reprogrammed to their initial state and consequently transformed into any cell type. These cells can be used to study disease, examine genetic variations and test new treatments.

The science behind iPSCs

The creation of iPSCs is based on the procedure of cell potency during mammalian

development. While the organism is still in the embryonic stage, the first cell developed is a totipotent stem cell, which has the unique ability to differentiate into any cell type in the

human body. “Totipotent” refers to the cell’s potential to give rise to all cell types and

tissues needed to develop an entire organism. As the totipotent cell grows, it develops into the pluripotent cell, which can differentiate into the three types of germ layers; the

endoderm line, the mesoderm line and the ectoderm line. The cells of each line then

develop into multipotent cells, which are derived into all types of human somatic cells, such as neuronal cells, blood cells, muscle cells, skin cells, etc.

Creation of iPSCs and organoids

iPSCs are produced through a process called cellular reprogramming, which involves the

reprogramming of differentiated cells to revert to a pluripotent state, similar to that of

embryonic stem cells. The process begins with selecting any type of somatic cell from the

individual (in most cases, the individual is a patient). Four transcription factors, Oct4, Sox2,

Klf4 and c-Myc, are introduced into the selected cells. These transcription factors are

important for the maintenance of pluripotency. They are able to activate the silenced

pluripotency genes of the adult somatic cells and turn off the genes associated with

differentiation. The somatic cells are now transformed into iPSCs, which can differentiate

into any somatic cell type if provided with the right transcription factor.

Although iPSCs themselves have endless applications in biosciences, they can also be

transformed into organoids, miniature three-dimensional organ models. To create

organoids, iPSCs are exposed to a specific combination of signalling molecules and growth factors that mimic the development of the desired organ.

Current applications of iPSCs

As mentioned earlier, iPSCs can be used to study disease mechanisms, develop personalised therapies and test the action of drugs in human-derived tissues. iPSCs have already been used to model cardiomyocytes, neuronal cells, keratinocytes, melanocytes and many other types of cells. Moreover, kidney, liver, lung, stomach, intestine, and brain organoids have already been produced. In the meantime, diseases such as cardiomyopathy, Alzheimer’s disease, cystic fibrosis and blood disorders have been successfully modelled and studied with the use of iPSCs. Most importantly, the use of iPSCs in all parts of scientific research reduces or replaces the use of animal models, promising a more ethical future in biosciences.

Conclusion

iPSCs are one of the most powerful tools of biosciences at the moment. In combination with gene editing techniques, iPSCs give accessibility to a wide range of tissues and human disorders and open the doors for precise, personalised and innovative therapies. iPSCs not only promise accurate scientific research but also ethical studies that minimise the use of animal models and embryonic cells.

Written by Matina Laskou

Related articles: Organoids in drug discovery / Introduction to stem cells