Mammals aren''t typically capable of regenerating organs as effectively as other vertebrates, such as fish and lizards. Today, Salk scientists have discovered a way to partially reset liver cells to new youthful states, allowing them to heal damaged tissue at a quicker rate than previously observed.
According to Juan Carlos Izpisua Belmonte, a professor at Salks Gene Expression Laboratory, and owner of the Roger Guillemin Chair, we believe that these approaches might be extended to replacing the whole organ itself. We believe that these findings could lead to the development of new therapies for infection, cancer, genetic liver disorders, and metabolic diseases such as nonalcoholic steatohepatitis.
The authors used Yamanaka factors to test if they might increase liver capacity and improve liver function while prolonging the lifespan of mice. This process involves partially reconverting mature liver cells to younger states.
According to Mako Yamamoto, a lab researcher in Izpisua Belmonte, the liver is more effective in repairing damaged tissue than most of our other organs. To research whether mammalian tissue regeneration might be enhanced, we used Yamanaka factors in a mouse liver model.
The Izpisua Belmontes team developed a short-term Yamanaka factor protocol, which used mice to receive treatment for one day. The experiment then tracked the activity of the partially reprogrammed liver cells by collecting periodic samples and closely monitoring how cells divided over several generations. Even after nine months, only a third of the mice lived time.
Yamanaka factors are truly a double-edged sword, according to Tomoaki Hishida, a former postdoctoral fellow at the Izpisua Belmonte lab and current associate professor at Wakayama Medical University in Japan. On the one hand, they have the potential to increase liver regeneration in damaged tissue, but the downside is that they can cause tumors. We were extremely pleased to discover that our short-term induction protocol has the good effects without the badimproved regeneration and no cancer.
While studying this reprogramming mechanism in a lab dish, a gene called Top2a is involved in liver cell reprogramming, which is highly active one day after a short-term Yamanaka factor treatment. Top2a is an enzyme that helps break up and rejoin DNA strands. This resulted in a 40-fold reduction in cellular reprogramming rates, leading to fewer young cells. This is still a future topic of research.
Izpisua Belmonte believes that understanding the molecular basis behind cell rejuvenation programming is still going ahead. "This is a serious obligation for developing effective and universal medical therapies as well as reducing the effects of human illness."