Tattooed mouse study reveals why ink is so hard to eliminate

Humans may have been getting themselves tattooed since the birth of civilisation but the biological reasons for their permanence are still being unravelled. A new study from French researchers has picked apart a crucial knot in this mechanism; one that could drastically improve the way tattoos are removed.

For a long time, tattoos were thought to be permanent because they stained fibroblast cells in the dermal layer of the skin. More recently, evidence has suggested that immune cells in the skin’s dermis – called macrophages – are responsible for the staining. These cells are drawn to the wound caused by the tattoo needle and eat up the pigment much like they would invading pathogens.

But how is the pigment passed on when those cells inevitably die? The researchers, led by Sandrine Henri and Bernard Malissen of the Centre d’Immunologie de Marseille-Luminy, set out to decipher this process by tattooing a genetically engineered mouse and observing what happened when they eliminated the macrophages in its skin.

The mouse’s genes made it possible for the scientists to kill the macrophages in its dermis. They tattooed the animal’s tail, confirmed the macrophages were indeed the only cells to take up the pigment, then killed off the macrophages. That would get rid of the tattoo, you’d logically expect. Instead of removing the tattoo, however, there were no visible changes.

(The tattooed tail before [left] and after [right] dermal macrophages have been killed. Credit: Baranska et al.)

The researchers concluded that, when the macrophages die, they release the pigment into their surroundings. Over the next few weeks, this pigment are taken up by new macrophages before it can disperse. Instead of being lost along with the dead macrophages, the tattoo instead enters a cycle of capture, release, recapture, keeping the skin’s staining continuous.

To show this happens with the normal decay of skin, not just for a mouse that’s had all of its macrophages suddenly eliminated, the researchers transferred a portion of the animal’s tattooed skin to another mouse. After six weeks, most of the pigment-laden macrophages belonged to the recipient, not the donor.

So how could all this help tattoo removal? Doesn’t the research only go to show that it’s very difficult to get rid of a tattoo, even if you kill the pigment-carrying macrophages? Bernard Malissen, a co-author of the study, tells Alphr that that the removal of macrophages could be used in combination with the kind of laser treatment currently used to remove tattoos.  

(Green tattoo pigment taken up by dermal macrophages [left], and released when the cells are killed [right]. The pigent will go on to be re-captured by new macrophages. Credit: Baranska et al.)

“Laser pulses lead to cellular lysis, fragmentation of the tattoo pigments and their elimination via lymphatic transportation,” explains Malissen. “Several cycles of laser treatment are required to achieve tattoo removal and some tattoos remain immune to full removal. These difficulties are generally accounted for by the fact that a fraction of the fragmented pigment particles remain at the tattooing site and are recaptured by neighbouring macrophages, a possibility formally demonstrated by our study.

“Tattoo removal can be likely improved by combining laser surgery with the transient ablation of the macrophages present in the tattoo area. Accordingly, the fragmented pigment particles generated using laser pulses will not have the possibility to be immediately recaptured by dermal macrophages, a condition increasing the probability of having them drained away from the skin via the lymphatic vessels.”

As well as tattoo removal, the research could be used to help treat hyperpigmentation conditions, where patches of skin become darker in colour than surrounding tissue. Malissen adds that, unfortunately, this technique could not be used to do the opposite and stop tattoos from wearing away: “Fading is likely due to the fact that during the successive capture-release-capture cycles, which we have described, minute amounts of released pigments are drained away from the skin.”

Still, if you regret that detailed drawing of S Club 7 on your lower back, you could soon have a better way to pretend it never happened.