Treating a tricky skin disease | Interviews – The Naked Scientists
Posted: December 20, 2019 at 4:46 pm
Imagine if your skin was so fragile that even the slightest knock caused it to blister and tear. This is the reality for people with a condition called epidermolysis bullosa. It occurs when a person inherits faulty copies of the genes that make the crucial skin protein collagen. But help may now be at hand,because Columbia University researcher Joanna Jackow has found a way to make stem cells, called iPS cells, from patients skin cells; edit the faulty genes in the stem cells, and use the now-repaired cells to grow new, healthy skin. It's the first step towards skin replacements for patients with these sorts of genetic skin diseases...
Joanna - Patients have an extensive blistering of the skin because they were born with this mutation. The skin starts to blister right after birth. These blisters are chronic wounds that are not healed, and these chronic ones convert to extensive scarring and, finally, with increasing age, the patients get a skin cancer called squamous cell carcinoma.
Chris - What's the approach you've taken to try to put this right?
Joanna - Using this magic genetic scissors called CRISPR, we can fix this mutation in cells called induced pluripotent stem cells, which are cells that we can generate from the patient's own cells. Because the cells have a potential of differentiation to any cell type we want, in our case skin cells, we can develop skin equivalents, which we called grafts, and these skin equivalents can be grafted onto the wounded areas of the skin.
Chris - So you're saying 'make some stem cells, fix the gene problem in those stem cells, and then grow new rafts of skin from the fixed stem cells so that you've got new skin to put on to the individuals with the condition?
Joanna - That's correct.
Chris - How do you go, though, from those "fixed" skin cells into actually making skin?
Joanna - Yes, we take the right cells now and put them together in a matrix called collagen, and the cells will grow into a normal skin that we called a skin-equivalent; and the skin equivalent can be grafted on the patients.
Chris - Have you tested this though, in the sense that: you've got these patches of skin-equivalents, do they survive in the long term and for instance, if you put them onto an animal in place of its own skin, do they work?
Joanna - Yes. We used for this immune deficient mouse model, which is a model which doesn't have immune system and will not reject this graft. And we've been testing the survival of this graft two months post grafting and we could demonstrate that the grafts survived and produced this protein that was missing in previously in the patient's skin.
Chris - In other words, the implication is, were you to do this in a patient, because it would be their own cells, there wouldn't be an immune problem. So you could just put these skin patches on in place of the individual's injured skin, and it should take over the function of their injured skin and give them a healthy working skin?
Joanna - Exactly. That's exactly what is the concept of our strategy.
Chris - Big problem though, when you consider how big a person is, I mean the surface area of a human that's, you know, metres squared of skin, isn't it? So is it feasible to actually do this on the scale of the entire body? Because you'd have to replace all their skin, wouldn't you?
Joanna - Yes, this is an excellent question and we've been already thinking of this. So, we would like to first cover the large wounds of the patient's body and we hope that, because we are deriving the skin equivalents from keratinocytes, that - hopefully - have also a population of stem cells. Eventually, these grafts can take over and cover the whole body of the patient.
Chris - Thing is, skin isn't just skin-producing cells, is it? There's hair follicles in there; there are more complicated structures, like sweat glands, as well. Those aren't going to be present in the grafts you make, are they?
Joanna - That's what we are thinking as a next step, to make more complex skin including all these very important components. As you mentioned, hair follicle and sweat glands. This is what we keep in mind in the future...
Continued here:
Treating a tricky skin disease | Interviews - The Naked Scientists
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