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Induced Pluripotent Stem Cells

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Induced Pluripotent Stem Cells (iPSC) are a special kind of stem cell that, unlike other kinds of stem cells we’ve talked about so far, are not actually found in the body. Instead, iPSCs are made in the lab!

Just as a quick review, stem cells are pluripotent when they can become any type of cell in the body when given the right signals and the proper environment. Induced pluripotent stem cells were first made in 2006 by Shinya Yamanaka and other researchers at Kyoto University in Japan. The researchers took normal, completely differentiated adult cells (also called somatic cells) and reprogrammed them to revert into a pluripotent state.

The cells were reprogrammed using a set of molecules known as transcription factors.

Let’s go over how transcription factors work. As we learned in our Basic Cell Biology Section, all cells have a nucleus which contains DNA, the blueprint that our cells use to make proteins; these proteins will eventually go on to serve various functions that together make an organism work. But how does this blueprint turn into proteins? It’s by the process often referred to as the central dogma of DNA.

DNA —> mRNA —> PROTEIN

DNA is first made into another similar substance called mRNA (messenger ribonucleic acid) which then leaves the nucleus and goes to the ribosome. The ribosome, as you will remember, is the organelle in the cell that makes proteins. Pretty much, the ribosomes will read the mRNA, which it will use as a set of instructions to make the protein that was coded for in the DNA all the way at the beginning of this process.

In the first step of this process, DNA is converted to mRNA by transcription. Now, your cells don’t need to make every single protein your DNA codes all the time, and not all cells make all types of protein. What genes and what parts of the DNA actually end up being transcribed to make protein is part of what makes cells different from one another— it’s why a cardiac cell is different from a cell in your liver and why those cells are different from cells in your muscles, even though every single one of them has the same DNA. Transcription factors are proteins that bind to the DNA and control whether or not a specific gene gets transcribed to make the protein that it codes for. Pretty much, you can add transcription factors to a cell to control whether genes are turned on or off.

In this case, Shinya Yamanaka and his team added 4 transcription factors: Oct4, Sox2, Klf1/4, and c-Myc. These factors control the expression of genes that are involved in making a cell pluripotent. The researchers used a retrovirus in order to deliver these factors.

A retrovirus is a virus that contains RNA. The virus will insert this RNA into the host cell that it infects. This RNA will then get converted into DNA that is inserted into the host cell’s genetic material, causing the cells to eventually express the genes that the retrovirus has delivered.

So, through the delivery of these four special factors, you can get an adult cell, like a normal everyday skin cell, to revert into a versatile pluripotent state where it can become any kind of cell you want it to. This was a pretty amazing discovery, and in fact, Shinya Yamanaka was awarded the Nobel Prize in 2012 for developing this technique.

Why are induced pluripotent stem cells so unique and such an important discovery?

Like with other pluripotent stem cells, iPSCs also offer the same potential for use in medicine, such as applications in the regeneration of organs and tissue and in understanding disease. Here are some reasons why iPSCs are different from other kinds of pluripotent cells.

1) iPSCs come from adult cells that are easily accessible, and they do not involve the destruction of an embryo, which certain individuals and groups of people may find unethical.

2) iPSCs provide a perfect genetic match for any patient because they come from the patient's own cells. Since you are reprogramming iPSCs from an adult cell, you could take this cell right from the patient you are treating, reprogram it to be an iPSC, and then make it into the kind of cell you need. This means that patients could receive transplants of tissue and cells without tissue matching and without as many potential rejection problems. These cells could also potentially be manipulated to fix disease-caused defects in the patient's genome before transplantation.

3) iPS cells can also be used in the lab in order to model genetic disease. iPSCs made from the adult cells of patients suffering from genetic disorders can be grown in the lab in order to learn more about how these diseases work and can also serve as a medium for the testing of drugs and other therapies

iPSCs aren't perfect just yet— they still have a couple of characteristics that cause them to be different from embryonic stem cells, and it is really hard to reprogram cells into iPSCs efficiently. But they still provide a great deal of promise for the field of stem cell research.