Cellular regeneration restores damaged liver tissue faster than ever
Mammals can’t typically regenerate organs as efficiently as other vertebrates, such as fish and lizards. Now, Salk institute for biological studies scientists have found a way to partially reset liver cells to more youthful states. This results, published in Cell Reports on April 2022, reveal that the use of reprogramming molecules can improve cell growth, leading to better liver tissue regeneration in mice. Approaches like this could be extended to replacing the whole organ itself. This findings could lead to the development of new therapies for infection, cancer and genetic liver diseases as well as metabolic diseases.
The authors previously showed how four cellular reprogramming molecules—Oct-3/4, Sox2, Klf4 and c-Myc, also called “Yamanaka factors”—can slow down the aging process as well as improve muscle tissue regeneration capacity in mice. In their latest study, the authors used Yamanaka factors to see if they could increase liver size and improve liver function while extending the health span of the mice. The process involves partially converting mature liver cells back to “younger” states, which promotes cell growth. The issue many researchers in the field face is how to control the expression of factors needed for improving cell function and rejuvenation as some of these molecules can cause rampant cell growth, such as occurs in cancer. In fact, Yamanaka factors are double-edged sword. On the one hand, they have the potential to enhance liver regeneration in damaged tissue, but the downside is that they can cause tumors. To circumvent this, a research team team used a short-term Yamanaka factor protocol, where the mice had their treatment administered for only one day.
The scientists made a second discovery while studying this reprogramming mechanism. A gene called Top2a is involved in liver cell reprogramming and is highly active one day after short-term Yamanaka factor treatment. When the researchers blocked the gene, which lowered Topoisomerase 2a levels, they saw a 40-fold reduction in cellular reprogramming rates, leading to far fewer young cells. The exact role that Top2a plays in this process remains a future area of research. There is still much work to be done before we can fully understand the molecular basis underlying cellular rejuvenation programming approaches. This is a necessary requirement for reversing the effects of human disease.
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