Turning back the clock to make old skin cells young again

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Dr. Diljeet Gill, photo courtesy Babraham Institute, Cambridge UK

Sometimes when I am giving public presentations people ask if stem cells are good for the face. I always say that if stem cells could help improve people’s faces would I look like this. It’s a line that gets a laugh but it’s also true. The ads you see touting stem cells as being beneficial for skin are all using plant stem cells. But now some new research has managed to turn back the clock for skin cells, and it might do a lot more than just help skin look younger.

Back in 2007 Japanese scientist Shinya Yamanaka discovered a way to turn ordinary skin cells back into an embryonic-like state, meaning those cells could then be turned into any other cell in the body. He called these cells induced pluripotent stem cells or iPSCs. Dr. Yamanaka was later awarded the Nobel Prize for Medicine for this work.

Using this work as their starting point, a team at Cambridge University in the UK, have developed a technique that can rewind the clock on skin cells but stop it less than a third of the way through, so they have made the cells younger but didn’t erase their identity as skin cells.

The study, published in the journal ELifeSciences, showed the researchers were able to make older skin cells 30 years younger. This wasn’t about restoring a sense of youthful beauty to the skin, instead it was about something far more important, restoring youthful function to the skin.

In a news release, Dr Diljeet Gill, a lead author on the study, said: “Our understanding of ageing on a molecular level has progressed over the last decade, giving rise to techniques that allow researchers to measure age-related biological changes in human cells. We were able to apply this to our experiment to determine the extent of reprogramming our new method achieved.”

The team proved the potential for their work using fibroblasts, the most common kind of cell found in connective tissues such as skin. Fibroblasts are important because they produce collagen which helps provide support and structure to tissues and also helps in healing wounds. When the researchers examined the rejuvenated skin cells they found they were producing more collagen than cells that had not been rejuvenated. They also saw signs that these rejuvenated cells could help heal wounds better than the old cells.

The researchers also noted that this approach had an effect on other genes linked to age-related conditions, such Alzheimer’s disease and the development of cataracts.

The researchers acknowledge that this is all very early on, but the fact that they were able to make the cells behave and act like younger cells, without losing their identity as skin cells, holds tremendous promise not just for conditions affecting the skin, but for regenerative medicine as a whole.

Dr. Diljeet concluded: “Our results represent a big step forward in our understanding of cell reprogramming. We have proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells. The fact that we also saw a reverse of ageing indicators in genes associated with diseases is particularly promising for the future of this work.”

Using reengineered human skin cells to treat COVID-19

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Investigators at Cedars-Sinai have identified a potential new therapy for COVID-19: a biologic substance created by reengineered human skin cells.   

In the study—co-funded by the California Institute for Regenerative Medicine (CIRM)—scientists found the substance stopped SARS-CoV-2, the virus that causes COVID-19, from reproducing itself. The substance also protected infected cells when tested in human lung cells.  

Although still in the early stages, the findings open the possibility of having a new therapy for COVID-19 patients, of which there are few. Current COVID-19 treatments primarily focus on preventing the virus from replicating. This new potential treatment inhibits replication but also protects or repairs tissue, which is important because COVID-19 can cause symptoms that affect patients long after the viral infection has been cleared. 

The potential therapy investigated in this study was created by scientists using skin cells called dermal fibroblasts. The investigators engineered the cells to produce therapeutic extracellular vesicles (EVs), which are nanoparticles that serve as a communication system between cells and tissue. Engineering these fibroblasts allowed them to secrete EVs—which the investigators dubbed “ASTEX”—with the ability to repair tissue. 

The study tested ASTEX by applying it to human lung epithelial cells, cells that line the pulmonary tract and are the targets of SARS-CoV-2 infection. They discovered that ASTEX prevented cells from launching an inflammatory process that could lead to cell death. Cells treated with ASTEX also made fewer of a type of protein called ACE that SARS-CoV-2 may use to infect cells. 

The team compared the new potential treatment with remdesivir, a drug currently used to treat COVID-19, and found that remdesivir did not inhibit production of ACE. Instead, remdesivir stops the virus from latching on to a protein called ACE2. ASTEX, therefore, may present another way to prevent the virus from entering cells. 

“We were surprised to find this potential therapy shuts down a novel pathway for viral replication and also protects infected cells,” said Ahmed G. Ibrahim, PhD, MPH, assistant professor in the Smidt Heart Institute at Cedars-Sinai and first author of the study. 

Investigators at Cedars-Sinai are planning future studies.  

The details of the potential therapy are published in the journal Biomaterials and Biosystems. Read the source article here