Science Interviews

Interview

Mon, 10th Aug 2015

Organ regeneration trigger found

Luis Garza, John Hopkins University

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Researchers are saying that they are on the brink of being able to kickstart the 2nd degree burns on handregrowth of hair follicles and even other bodily organs. Scientists have discovered a trigger - in the form of short pieces of genetic material called double stranded RNA - which switches on an immune pathway that induces stem cells to rebuild organs like they do in a developing baby. Done in the skin, it could help victims of severe burns. Luis Garza made the discovery at Johns Hopkins University in the USA, and explains to Chris Smith...

Kat - First this week. Researchers are saying theyíre on the brink of being able to kick start the regrowth of hair follicles and even other bodily organs. Scientists have discovered a trigger in the form of short pieces of genetic material, called double-stranded RNA, which switches on an immune pathway inducing stem cells to rebuild organs, just like they would do in a developing baby. Done in the skin, it could help victims of severe burns. Louis Gaza made the discovery at Johns-Hopkins University in the US.

Louis - When I was a resident studying medicine. All of my teachers taught that it was impossible to grow a new hair follicle if you destroy the entire thing in an adult. And yet, other people before us, and we in this paper show that you indeed can do that. And so, it does create hope. In the same way that I was taught that you canít grow a new hair follicle, now people are taught we canít grow a new limb. But maybe, that might become a possibility.

Chris - How did you do this then, to regrow hair follicles? What was the actual experimental model that you set up?

Louis - We had two sets of mice. We do these very large wounds down to the depth of muscle. So, we remove all of the skin. One set of mice have poor ability to regenerate which is kind of currently the way we think a lot of humans are. And then the second strain of mice was a very good regenerator, so we would do the exact type of wound, and instead of having a pure scar, they would have a lot of hair follicle regeneration. So, we did these gene arrays where we query, ďWhatís the difference between the ones that do regenerate very well and the ones that donít?Ē

Chris - And was there a unique gene signature that appeared to be responsible for the difference in the healing?

Louis - Yeah. When we did statistics, we found a very significant signature to show that this pathway which is part of our innate immune pathway that I can explain. There are these receptors that were originally evolved to sense invading organisms that might try to cause an infection. And we found one of the elements of this ancient immune system in our mice that regenerate very well.

Chris - What is turning on that ancient arm of the immune system then in these regenerating mice? Is that the damage that then triggers that immune response that then in turn makes the skin grow better and makes new hair follicles come along?

Louis - Yeah. Itís just as you said - It is damage. This is a really fun intellectual question to say Ė how does your body know it when itís been hurt? It turns out this ancient immune system also senses damage and that we find a strong signature for that.

Chris - Now the killer question then. If you take that pathway and you induce that effect in the mice that donít normally regenerate very well; in other words, you super load them with more of that immune response that the good regenerators have. Can you turn the bad regenerators into good regenerators?

Louis - Yeah. We were able to do that. Yes. We could significantly increase the amount of regeneration in our bad regenerating mice by giving them these compounds that activate their innate immune system.

Chris - What are those compounds?

Louis - The compound is double stranded RNA. Scientists used to believe that double stranded RNA was only present in viruses, for example, like the measles virus. And that this innate immune pathway is the receptor to tell your body, ďHey! A virus has attacked!Ē But now, we know that itís very likely that double stranded RNA is also formed during damage and that the double stranded RNA then is activating itís receptor, and then thatís whatís turning on the regeneration and turning on stem cells.

Chris - Given youíve made this discovery then, and you can supply these chemicals, including this double stranded RNA signal that is the stimulus for this. Do you think then we are on the path now to being able to provision a human with these signals to make good damage and could you, for instance, make a bald person hairy again?

Louis - Yeah. Weíre really excited about this. And the very interesting part of this story is that we think that itís, like a lot of discoveries, itís already being used in ways we didnít predict. For example, men and women who want to look younger and go for rejuvenation and visit their local cosmetic dermatologist, and receive laser treatment or receive dermabrasion, or receive micro-needles for rejuvenation of their facial skin. Itís very likely that the one thing that unifies all these very different methods of rejuvenation is damage, and that itís by activating the same tall three double-stranded RNA pathway that people are receiving benefits when they go to their cosmetic dermatologist even now. So the exciting question that our work raises is whether we can reduce the damage we have to do by instead just directly giving these agents like double-stranded RNA and save people the suffering of having to go through these treatments. The other main application of this could be in scar victims. So, people whoíve had burns, for example, where we think by creating new hair follicles, weíll be able to restore the skin to the way it normally is which is dense with hair follicles - even where we canít see them, for example, on the face.

Kat - That was Louis Gaza, and heís just published that work in the journal, Stem Cell.

 

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