'Regrow limbs' claim is premature

A genetic discovery means that “damaged human limbs could one day regrow by themselves”, according to the Daily Mirror. The reported research found that switching off a particular gene in mice meant that they could grow healthy tissue to replace tissue that was missing or damaged.

This study highlights a role for this gene, called p21, in tissue regeneration in mice. However, while many biological pathways are similar across different species, there may still be differences. Therefore these findings in mice will need confirmation that they apply in human cells and tissues too.

The healing of a wound is a complex process, and a number of factors will play a contributing role. This research provides a better understanding of the process and may contribute to the development of medical approaches to improve wound healing. However, such developments will take time, and we are still a very long way off being able to regrow entire human limbs.

Where did the story come from?

Dr Khamilia Bedelbaeva and colleagues from the Wistar Institute in Philadelphia and Washington University carried out this research. The study was funded by the US National Institutes of Health and several research support foundations, including the Harold G. and Leila Y. Mathers Foundation, the F.M. Kirby Foundation and the W.W. Smith Foundation. The study was published in the peer-reviewed scientific journal Proceedings of the National Academy of Sciences USA.

The Daily Mirror, Guardian, and Daily Express have reported on this complex research. The_ Guardian_ provides good overall coverage of it, while the Mirror and Express focus more on the possibility of regrowing lost limbs in humans, which is a distant hope. The Express does include a quote from the researchers saying that to get major organs or limbs to repair “will need decades of work”.

What kind of research was this?

This was animal research attempting to identify genes that are involved in the regeneration of damaged or missing tissue. Some animals, such as salamanders, can regenerate different organs, tissues, and even limbs if they are lost or damaged, without leaving scars.

This ability is generally not seen in mammals, but one strain of mice called the “Murphy Roths Large” (MRL) mouse can partially regrow amputated toes and grow tissue to close puncture wounds to their ears without scarring. The researchers investigated this strain to see how they differed from other strain that did not have this healing capability.

This type of study helps researchers to understand the biology of tissue regeneration. However, although many biological pathways share similarities across different species there are a number of differences. This means that findings in mice may not be directly applicable to humans, and any findings would need to be confirmed using tests on human tissue. Equally, even if laboratory tests on human cells confirm the presence of a particular biological pathway, this does not necessarily mean that this knowledge will lead to a successful treatment for human disease.

What did the research involve?

The researchers took uninjured skin cells from MRL mice and from normal mice and grew them in the laboratory. They then compared the characteristics of these cells to see how they differed throughout their cellular lifecycle. The study particularly focused on how they prepare for and undergo cell division, as these functions are important in repairing and regrowing damaged or missing tissue.

The researchers also looked specifically at the activity of a gene called p21, which regulates whether cells are able to divide and plays a role in stopping damaged cells from dividing. They looked to see whether wound healing in mice that had been genetically engineered to lack the p21 gene differed from wound healing in normal mice.

What were the basic results?

The researchers found that uninjured skin cells of MRL mice had characteristics similar to the cells of animals that are able to regenerate tissue successfully, such as salamanders. These skin cells also had similarities to mammalian stem cells, which can also regenerate tissue.

In particular, a greater proportion of the MRL skin cells had copied their DNA in preparation for division into two cells if needed; for example, if they needed to regenerate lost or damaged tissue. Cells that do this are more likely to be able to regenerate quickly. In the non-MRL mice, fewer skin cells had reached this stage.

The p21 gene, that can stop cells dividing in unfavourable conditions, is not active in mouse embryo stem cells. The researchers found that this division-blocking gene was also inactive in the MRL cells. Mice genetically engineered to lack the p21 gene showed enhanced healing of damaged ear tissue akin to that found in MRL mice, rather than the limited healing ability of normal mice.

How did the researchers interpret the results?

The researchers concluded that there is a link between how cells prepare for and undergo cell division (the cell cycle) and tissue regeneration.

Conclusion

This study illustrates a role for the p21 gene in tissue regeneration in mice. Although many biological pathways share similarities between different species, there may also be distinct differences. Therefore findings on p21 in mice will need confirmation in human cells and tissues. Wound healing is a complex process, and even if p21 has a role in human healing a number of additional factors will also play a role.

This study may lead to a better understanding of the human healing process. Realistically, it would be more likely to help in the development of treatments to aid wound healing rather than growing back whole limbs. However, even developing a treatment for wound healing based on this research would take a long time, and unfortunately such a treatment may eventually prove to unfeasible or unsuccessful.