From Amphibian to Mice, Limb regeneration

It is commonly known that salamanders and newts have amazing regenerative abilities. If their tail or even a limb gets lobed off they are capable of regenerating a brand new one. According to the article in Nature entitled “Muscling in on limb regeneration” researchers have found a way to duplicate this regenerative ability in mice tissue. This research was lead by Helen Blau, a regenerative biologist at Stanford University of Medicine in California.

Previously the regenerative ability was attributed to stem-cells that remain in adult tissue, but the minimal number of these stem-cells in newts begs to differ. Now biologist lean toward the following conclusion: “in vertebrates endowed with regenerative ability, muscle cells surrounding injured tissue temporarily regress to a more primitive state, re-entering the cell cycle and then proliferating to produce more muscle cells.” The key factor in specialization of the muscle cells is retinoblastoma protein, Rb for short. When the Rb gene is suppressed in the muscles cells it sends the cells into the cell cycle again. But this process doesn’t work in mammal muscle cells.

Blau proposes the following: “that in mammals, an additional mechanism may have evolved atop the Rb pathway to confer tumour suppression. Unlocking regeneration in mammalian tissues may involve interfering with that pathway too.” The research team focused on a tumor-suppressing gene called Arf, which is present in mammals but not the regenerating vertebrates. Blau and her staff temporarily knocked down Arf and Rb in cultured mouse muscle cells. After doing this they found the treated cells re-entered the cell cycle and they began proliferating. The results were as follows: “When genes’ activities were restored, the cells returned to their differentiated state. Newly generated muscle cells transplanted into living mice were able to integrate into the animals’ muscle tissue.”

There are many questions and complications that arise with this research. One problem that arises is if the tumor suppressing gene is shut off, could this lead to tumors forming. Blau incorporation with Jason Pomerantz, a reconstruction surgeon from the University of California, believes that the tissue could be resolved by treating it as explants, and then implanted onto an organism. Another suggestion is to use drugs blocking the two genes injecting them into the spot that needs regenerated.

There are several unknowns that remain, which were pointed out in this article by Ken Poss, a cell biologist at Duke University Medical Center in California. Poss says, “regernation large chunks of tissue may involve recreating the connective-tissue scaffolding on which muscle cells grow—a step that’s not part of this technique.”

Nature paper: http://www.nature.com/news/2010/100805/full/news.2010.392.html

Published online 5 August 2010 | Nature | doi:10.1038/news.2010.392

Image from the Nature paper