stem cells in their environment

Malcolm Maden – The astonishing healing capabilities of axolotl & the African spiny mouse

05 December 2013
By Christine Weber

Professor Malcolm Maden has always been interested in regeneration. In search of a suitable model organism to study this subject he therefore turned to axolotl; a rather logical step considering the remarkable healing skills these little amphibians can pride themselves on. Scar-free regeneration of whole limbs is just one of the astonishing feats of axolotl. However, as Prof Maden dryly concluded, not many organisations or funding bodies were as enthusiastic about the research possibilities opened up by

this fascinating species as he was, and funding was rather difficult to obtain. Still, he got a long way diving into the molecular details of the unique regeneration capabilities of axolotl.

In his talk at King's last week he also posed the interesting question why wounds in adult mammals usually heal with scars whereas in axolotl, skin, limbs, brain, heart and other organs recover completely and without a trace of the previous injury. Some potential explanations his lab found in axolotl were a reduced haemostatic response; lower numbers of certain immune cells; a swifter closing of the wound-epithelium and different collagen depositions. In this aspect, axolotl seem to resemble embryonic mammalian tissue which also exhibits scar-free wound healing – a controversial hypothesis that Professor Maden's lab set out to test.

However, having the genetic makeup of an entirely different phylogenetic class of vertebrates it remains to be seen how much of axolotl's unique regeneration properties can potentially be transferred to humans. So when Ashley Seifert – back then a member of Professor Maden's lab, now a PI himself - heard about a mysterious African spiny mouse (Acomys sp.) which was said to escape its predators by shedding its skin and regenerating it afterwards, he couldn't resist and travelled to Kenya to find out more. And indeed, his studies show that these mice are not only able to completely repair skin wounds in a scar-free manner, they also regenerate hair follicles and appendages in the wound bed. They can even heal large circular ear holes with complete restoration of hair follicles, dermis and cartilage. The skin of spiny mice is unusually weak and only very small amounts of tension are required to tear it apart – making it possible for these mice to shed it when grabbed by a predator.

African spiny mice can shed up to 60% of the skin on their backs.
Source: Seifert Lab
By comparison, the skin of the normal lab mouse mus musculus is tougher but heals less quickly and cannot regenerate hair follicles or appendages. It also grows scar tissue, as does human skin. The unique type of tissue repair found in the spiny mouse has, in fact, not been seen before in any other mammal. Still, researchers believe that the spiny mouse could prove useful in identifying mechanisms to promote scar-free regeneration in humans as well. Acomys is more closely related to homo sapiens than axolotl and corresponding genes that drive Acomys regeneration could potentially also function in humans. Ashley Seifert thinks it unlikely that the spiny mouse has evolved an entirely new method of tissue repair. It probably utilises similar regeneration genes as amphibians, which have been switched off in mammals during evolution.

It will be a challenge to identify the molecular and genetic mechanisms at work in this unique rodent, and it will be an even greater task to re-awaken those abilities which the organism once, in an earlier evolutionary or developmental stage, already possessed. Professor Maden's and Seiferts' labs are certainly on a promising journey.

References

•  Ashley W. Seifert, Stephen G. Kiama, Megan G. Seifert, Jacob R. Goheen, Todd M. Palmer & Malcolm Maden (2012)  Skin shedding and tissue regeneration in African spiny mice (Acomys); Nature 489, 508–510

•  Regenerative biology: Skin, heal thyself Nature News & Views

•  African spiny mice can regrow lost skin Nature News & Views

Professor Malcolm Maden... sadly not the outfit he wore for the seminar though
Source: Malcolm Maden

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