Partial Reprogramming Improves Liver Regeneration in Mice

While much of the focus on cell reprogramming these days is upon the ability of reprogramming factors to produce epigenetic and functional rejuvenation, there are other lines of research. Here, researchers show that short-term exposure to reprogramming factors can improve liver regeneration in mice. This is interesting, but as noted the liver is a very regenerative organ in comparison to other mammalian tissues, and the mechanisms of regeneration may be distinct from other tissues. Thus the ability to improve regeneration in the liver via reprogramming may or may not generalize to other organs.

Researchers 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. To circumvent this, researchers used a short-term Yamanaka factor protocol, where the mice had their treatment administered for only one day. The team then tracked the activity of the partially reprogrammed liver cells by taking periodic samples and closely monitoring how cells divided over several generations. Even after nine months - roughly a third of the animal's life span - none of the mice had tumors.

"Yamanaka factors are truly a 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. We were excited to find that our short-term induction protocol has the good effects without the bad-improved regeneration and no cancer."


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