Losing a gene, regaining lost tissue

Tissue regeneration may be common in certain species but is rare in mammals. Typical mammalian healing involves scar formation, and scar tissue is quite different from the original tissue that it replaces. Regeneration, on the other hand, involves formation of a blastema, a group of cells capable of rapid growth that recreates missing tissue.

Regeneration is not completely absent in mammals: in 1996, Ellen Heber-Katz accidentally discovered that the MRL mouse strain was capable of tissue regeneration. Since then, this ability has remained something of a mystery. But now Heber-Katz (The Wistar Institute, Philadelphia, PA) and her colleagues have identified what makes MRL mice into 'healers': inactivation of the protein p21, a cell-cycle regulator.

The scientists then tested wound healing in mice lacking expression of p21 and found that these mice were also capable of tissue regeneration (Proc. Natl. Acad. Sci. USA 107, 5845–5850; 2010). The results link tissue regeneration with cell-cycle checkpoint control. P21 is also associated with DNA damage repair and oncogenesis. Mice lacking p21 expression did have more DNA damage than normal mice but so far have not shown a higher cancer incidence.

It's not yet clear how these findings may apply in humans, but future studies may investigate whether temporary inactivation of p21 accelerates healing.

Fixing injured hearts

Though humans maintain some ability to regenerate heart muscle cells throughout life, after a non-fatal heart attack, heart cells generate little or no significant new, healthy muscle tissue. Instead, the damaged heart generates stiff scar tissue. Unlike humans, zebrafish can regenerate their own damaged heart tissue. Now, US researchers have identified key cells involved in zebrafish heart repair. They hope that a better understanding of how this regeneration occurs can be used to help people with injured hearts.

In this study, Kenneth Poss of the Duke University Medical Center (Durham, NC) and colleagues cut off part of the ventricle in the hearts of zebrafish and tracked the activity of particular cells and the progeny of these cells (Nature 464, 601–605; 2010). They found that this injury causes increased expression of the gene gata4 in a group of heart muscle cells, thereby triggering regeneration. Within 4 weeks after the injury, electrical conduction between the new and previously existing heart muscle cells was restored, indicating that this new tissue was healthy.

The authors note that further research is needed to see how other zebrafish heart cell populations contribute to regeneration following injury. They also plan to study the effects of manipulating gene function or expression on zebrafish heart cell regeneration.

Animal research bias

According to a recent study, animal trials of potential stroke treatments are more likely to be published if they have positive results than if they have negative results. This is the first time that researchers have quantitatively determined whether any type of laboratory animal studies have this publication bias.

For their analysis, Malcolm Macleod of the University of Edinburgh (UK) and colleagues used the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Stroke, a database set up in 2004 to try to improve the translation of animal research results into clinical trials. The team looked at 525 studies, which included a total of 1,359 experiments testing 16 types of stroke treatments (PLoS Biol. e1000344; 2010). They found that only 1.2% of these publications reported no significant findings. Statistical analysis suggested that this publication bias overestimates the efficacy of these stroke treatments by about 30%.

Earlier recognition of a considerable publication bias in clinical trials led to the use of clinical trial registration systems. In their article, Macleod and colleagues suggest that the creation of a central register of animal experiments that have been carried out could help people writing reviews to assess “the extent to which publication bias may confound their conclusions.”