Reprogramming technology allows faster repair of damaged liver tissue

"We are excited about progress in repairing damaged liver cells, because one day, methods like this could be extended to replace the entire organ itself," said corresponding author Juan Carlos Izpisua Belmonte, a professor in the Salk Gene Expression Laboratory

Mammals generally cannot regenerate organs as efficiently as other vertebrates such as fish and lizards

The authors have previously shown that four cellular reprogramming molecules -- Oct-3/4, Sox2, Klf4, and c-Myc, also known as "Yamaka factors" -- can slow the aging process in mice and improve muscle tissue regeneration

"Unlike most of our other organs, the liver is more efficient at repairing damaged tissue," said co-first author Mako Yamamoto, a researcher in Izpisua Belmonte's lab

The question facing many researchers in the field is how to control the expression of factors needed to improve cell function and rejuvenation, as some of these molecules can lead to rampant cell growth, such as cancer

"The Yamanaka factor is really a double-edged sword," said co-first author Tomoaki Hishida, a former postdoc in Izpisua Belmonte's lab and now an associate professor at Hoyama Medical University in Japan

While studying this reprogramming mechanism in a lab dish, the scientists made a second discovery: A gene called Top2a, involved in reprogramming liver cells, was highly active in the day following short-term Yamanaka factor treatment

"There is still a lot of work to be done before we fully understand the molecular basis of how cells are programmed to regenerate," said Izpisua Belmonte

Tomoaki Hishida, Mako Yamamoto, Yuriko Hishida-Nozaki, Changwei Shao, Ling Huang, Chao Wang, Kensaku Shojima, Yuan Xue, Yuqing Hang, Maxim Shokhirev, Sebastian Memczak, Sanjeeb Kumar Sahu, Fumiyuki Hatanaka, Ruben Rabadan Ros, Matthew B.