Chandan Sen, a researcher at Ohio State, holding up the Tissue Nanotransfection Device

What if I told you that you had roughly 35 billion cells that could be reprogrammed to help save your failing kidney, or be altered to help your wounds heal faster and stronger? Due to the newfound ability to transform skin cells to iPSCs (induced pluripotent stem cells), that and much more is now possible. 

The average NFL football stadium has a seating capacity of 69,000 people when fully packed. As of January 2019, more than 113,000 people were documented being on a waiting list for a life-saving organ transplant. That’s almost twice the capacity of the football stadium, and that’s only the documented cases. There could hundreds, or even thousands more just in the United States alone. For years, scientists and researchers have tried to come up with a solution for organ shortages around the world, but to no avail. However, a new organ manufacturing technique involving skin cells has come to light, and it may be the miracle we were all waiting for. 

Skin is a remarkable part of our bodies. Not only is it our largest organ, but it also serves multiple purposes. It protects from outside factors such as sunlight or some light physical damage, helps us feel from the nerves embedded in them, and helps us cool down through the sweat glands. Skin is composed of three parts: the Epidermis, the Dermis, and the subcutaneous layer. The Epidermis is composed of four layers, the top two of which are a cycle of dead and replacement cells. Melanin comes from the last layer of the Epidermis. The Dermis layer is made up of blood vessels and provides the skin’s flexibility. Lastly, the subcutaneous layer is just fatty tissue. 

The discovery of being able to genetically alter skin cells to have them become one of three types of induced pluripotent stem cells (iPSCs), which are just essentially stem cells of the embryo, placenta, or extra-embryonic tissue, is a modern discovery that is fairly well known in the scientific community. But researchers at Ohio state have taken the concept of iPSCs to the next level. They have managed to create a trial involving a device called the Tissue Nanotransfection device (TNT), a noninvasive tool that can alter skin cells with just a touch, and transform them to the intended type of cell, including organ cells. The test subjects for this experiment were a mouse and a pig with injured legs that did not have blood flow. Within a week of applying the Tissue Nanotransfection device, active blood vessels were found in both the test subject’s legs, and within two weeks the legs were saved. But the use of the TNT device goes beyond just organ manufacturing; nerve cells were also formed by transforming skin cells to help mice who had strokes to recover. 

The key to unlocking all of this was the implementation of skin cells into iPSCs. One of the most famous origins of this technology was Dr.Yossi Buganim and his team at The Hebrew University of Jerusalem. Together they found a set of five genes that once inserted into the skin cells, would alter them into the iPSCs cells, the cells that create fetuses. When studying the structure of the skin cells, they found out that once the set of genes is introduced into the skin cells, the cell first “loses” its identity and then gains one the function of one of the three embryonic cells, known as an iPSCs

In the short time that the technology for the iPSCs has been available, modifications to make it safer and more effective has begun. One of the reasons that the induced pluripotent stem cell transformation works is from its use of transcription factors. Transcription factors are proteins that regulate the rate in which DNA is converted to its counterpart RNA. In previous trials, the transcription factors generally used are called Klf4 and c-Myc. Researchers Wenwen Deng, Cao Xia, Chen Jingjing, and Zhang Zhijian replaced those transcription factors with microRNA 302-367, which was chosen out of seven other compositions, and tested in mice with compromised immune systems. After gathering the data, the results showed that the change in transcription factors created a smaller chance of genetic modification but also helped the reprogramming efficiency to go up tremendously. 

But the benefits of iPSCs don’t just stop at organ manufacturing. Scientists from Stanford University turned skin cells into blank iPSC cells and had them grow in monolayers (single layer, sometimes in Petri dishes). After putting them in a dish and seeing colonies form, they added a mixture of compounds as an attempt to try to make them form immature brain cells. Eventually, a formation of neurons and astrocytes (star-shaped cells found in the brain) was found within the dish. Once the scientists cut the cells in half they found a network that is similar to the cortex of the human brain. Upon further testing, they found that 80 percent of the neurons in the cells could fire when stimulated by the scientists and 86 percent contributed in the activity that resembles what is normally found in the brain. A possible outcome of this experiment is being able to attempt to understand the development of the brain and its disorders in a different and closer way, by being able to manipulate its growth and process.

Although fairly early in development, skin cells are becoming much more involved in modern medical research. The abundance, as well as malleability of the cells, could be the key to solving many of the problems that affect our health today, as well as being able to study organs and parts that we couldn’t before. Who knows, maybe the cure to cancer could lie in the palm of our hand. Quite Literally. 

By: S.Singh

References:

Andrew, Elise. “Scientists Grow Mini Brains From Patient Skin Cells.” IFLScience, IFLScience, 11 Mar.2019, https://www.iflscience.com/brain/scientists-grow-mini-brains-patient-skin-cells/

Deng, Wenwen.Xia, Cao, Jingjing, Chen.Zhijian, Zhang “OOPS.” Digital Object Identifier System, 2015, doi.org/10.1021/acsami.5b06768.

“Embryo Stem Cells Created From Skin Cells.” ScienceDaily, ScienceDaily, 2 May 2019, www.sciencedaily.com/releases/2019/05/190502143437.htm.

Geoshen. “NFL Stadiums Ranked by Seating Capacity.” NFL Stadiums Ranked by Seating Capacity, geoshen.com/posts/nfl-stadiums-ranked-by-seating-capacity.

Ohio State University. “Ohio State Researchers Develop Regenerative Medicine Breakthrough.” Ohio State Researchers Develop Regenerative Medicine Breakthrough, The Ohio State University, 12 July 2018, news.osu.edu/ohio-state-researchers-develop-regenerative-medicine-breakthrough/.

“Organ Donation: Facts vs. Fiction.” UCI Health, UCI Health, 23 Apr. 2019, www.ucihealth.org/blog/2019/04/organ-donation.

“Transplant Trends.” UNOS, unos.org/data/transplant-trends/.

Image Credits:

The Ohio State University Wexner Medical Center, Researcher Chandan Sen with the nanotechnology-based chip designed to deliver biological “cargo” for cell conversion, Ohio State News, https://news.osu.edu/ohio-state-researchers-develop-regenerative-medicine-breakthrough/