How Can Induced Pluripotent Stem Cells Benefit Patients?

 by  Christine Zhou

Every cell in the body has the same genetic instructions. So what makes a heart cell different from a liver cell? The two cells express different sets of genes. Likewise, a stem cell turns on specific sets of genes to differentiate into another cell. [1]

In terms of their capacity for proliferation, stem cells can be classified as totipotent, pluripotent and multipotent. Totipotent cells can give rise to both the placenta and the embryo. Embryonic stem cells are pluripotent cells which can differentiate into all cell types in an adult. As the embryo grows into adult, these pluripotent cells develop into specialised, multipotent stem cells, which are responsible for replacing damaged and dead cells in the body. [2]

However, these adult stem cells, also known as tissue-specific stem cells, can only differentiate into unipotent cells of the residing tissue. [3] These cells are mainly found in various regions of the adult organism, such as bone marrow, skin, eyes, viscera and brain, generally for repair. [4] They have lost the ability to grow into all the cell types like pluripotent cells. As a result, adult stem cells have a determined cell type and cannot be changed into tissues that differ from the ones that they came from. 

Since multipotent stem cells form from pluripotent stem cells, is it possible to revert the adult stem cells to the embryonic cells that can differentiate into different cell types? If this can be achieved, hence scientists came up with Induced Pluripotent Stem Cells (IPSCs). These cells are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes. [5] 

IPSCs are made by taking a mitotic cell - usually a skin cell - from a patient's body. The cell is then treated by specific transcription factors: Oct4, Klf4, Sox2 and c-Myc proteins. They are introduced into the cell using viruses that can deliver the genes in a way similar to how a virus causes infection in a cell. The genes cause the cell to produce specific proteins. These proteins enter the nucleus and act on the cell's DNA. This causes the cell's DNA to convert the cells into pluripotent stem cells - Induced Pluripotent Stem Cells. [16] Then changing the culture conditions of these IPSCs can stimulate these cells to differentiate into a variety of cell types. (Figure 1)

IPSCs have many benefits for patients. For example, patients with severe burns can have their skin grown in the laboratory and grafted onto them later. One limitation of current skin grafting methods is that when transplanting the skin from one area of the body to the burn section structures such as hair follicles and blood vessels are lost. By growing the skin from the pluripotent stem cells, the skin grafts will have hair follicles and blood vessels, therefore the survival rate of the new skin can be improved. 

People suffering from organ failure can also benefit from IPSCs. The shortage of organs to treat organ failure has led to doctors looking for alternative sources and the current solution is humanised pig organs. However, with IPSCs, patients will be able to grow another organ with their own cells and DNA, which can thus reduce their dependence on organ supply and they do not need to worry about organ rejection or incompatibility when the organ is transplanted to them. 

Lastly, IPSCs can be transplanted into the pancreas of diabetic patients. These cells can differentiate into pancreatic cells to produce insulin, thus reducing the need and reliance on long-term medication. 

As IPSC technology is a complex process, it is without a doubt that it will not be 100% efficient. Experiments have shown that this procedure may not always be successful and harmful mutations can occur instead, leading to a higher risk of genetic diseases such as cancer. Also, IPSC is an expensive process and the cost may be greater than the merits it can bring. 

There are also ethical concerns about IPSCs. It is possible to create an egg cell and a sperm cell from normal skin cells to create a human being. Some people may see this as a problem as human embryos can be created. Meanwhile, with the advancement of technology, it will be possible to edit the genes in the sperm or egg cells to produce human beings with desirable traits. [7] 

Although IPSC comes with high risks, we cannot deny the progress it can bring to medical therapeutic advancements. We can have strict controls to prevent people from abusing this technology to make sure it can benefit humans. 

References: 

[1] Watson, S. and Craig Freudenrich, P.D. (2023) How stem cells work, HowStuffWorks Science. HowStuffWorks. Available at: https://science.howstuffworks.com/life/cellular-microscopic/stem-cell4.htm (Accessed: April 24, 2023). 

[2] Nature news. Nature Publishing Group. (2023) Totipotent stem cells articles from across Nature Portfolio. Available at: https://www.nature.com/subjects/totipotent-stem-cells (Accessed: April 24, 2023). 

[3] Current Topics in Developmental Biology. (2010) Adult Stem Cell. Available at: https://www.sciencedirect.com/topics/medicine-and-dentistry/adult-stem-cell (Accessed: April 24, 2023). 

[4] Mariano, E.D. et al. (2015) Adult Stem Cells in neural repair: Current options, limitations and perspectives, World Journal of stem cells. U.S. National Library of Medicine. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369503/ (Accessed: April 24, 2023). 

[5] UCLA Broad Stem Cell Research Centre. (2023) Induced Pluripotent Stem Cells (iPS)

 Available at: https://www.researchgate.net/profile/Suely-Marie/publication/274258657_Adult_stem_cells_in_neural_repair_Current_options_limitations_and_perspectives/links/552257840cf29dcabb0d4105/Adult-stem-cells-in-neural-repair-Current-options-limitations-and-perspectives.pdf (Accessed: April 24, 2023). 

[6] University of California Television. (2019) Making Pluripotent Stem Cells. [Video] Available at: https://www.youtube.com/watch?v=2zoLUmZyxLk (Accessed: April 24, 2023). 

[7] NIE SINGAPORE. (2018) Induced Pluripotent Stem Cell iPSC. [Video] Available at: https://youtu.be/YdjQz4urDjM (Accessed: April 24, 2023). 

[8] IPSC21. (2020) IPSCs - induced pluripotent stem cells. Available at: https://www.ipsc21.com/ipscs/ (Accessed: April 24, 2023).