History of epidermal stem cell use in the clinical setting

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Published: 14 Dec 2012
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Prof Michele De Luca - University of Modena e Reggio Emilia, Modena, Italy

Prof Michele De Luca talks to ecancer at the 2012 ASH annual meeting in Atlanta, Georgia about the evolution of stem cell use in the clinical setting.

ASH 2012

History of stem cell use in the clinical setting

Professor Michele De Luca – University of Modena e Reggio Emilia, Modena, Italy

We started working with stem cells many years ago; it was the middle ‘80s when I was back from the US, I was in Boston, Howard Green’s lab, and we started in Europe to grow epidermal cells for skin burns, severe skin burns. From that point we developed ourselves new therapies; the most important are the regeneration of the corneal epithelium in massive chemical burns of the eye and lately also gene therapy of genetic skin diseases like epidermolysis bullosa by means of genetically modified epidermal stem cells that can be transplanted back into the patients.

As I said, when I was a post-doc a couple of centuries ago, I was in Howard Green’s lab in Boston in Harvard and Howard was the guy that was really developing the technology of growing epidermal stem cells for skin burns. Few people know that that has been the first clinical application of any cultivated, cultured stem cell. Therefore, from that point then I developed my own career together with my main collaborator, Grazielle Pellegrini, to develop all this new technology for other types of stratified epithelia, including the cornea. But we are working also on the regeneration of other squamous epithelia like the urethral epithelium, the oral mucosa, but it is still at the pre-clinical level. It’s not the method but it’s the way that we try to bring things from the basic science to the lab with very vigorous basic science behind. I believe, probably, that is what is missing these days where there is a sort of hysteria of bringing any type of stem cell, or supposed stem cells, into the clinics without an appropriate understanding of the basics, of the cell biology behind those stem cells. We have many examples of this.

So the reason why I’m in the haematology meeting is because I think that the message was that the use of the particular stem cells paradigmatic show how the translational medicine should be done with rigorous basic science behind.

Can you talk about the possible clinical settings for the use of stem cells?

This is an important question because there are two clinical settings. There’s a clinical setting where you have an epidermal defect limited, like chronic leg ulcers or a limited area of the body where you have no epidermis. In this case you can stimulate resident stem cells to migrate and grow. In order to do this you don’t really need stem cells, you need a biological medication that can be done by protein extracts or allogeneic epidermal cultures that stimulate the migration and the healing of the wound. The second clinical setting, that is the type of patients I’m dealing with, you have really destruction of a massive area of the skin. Like, for instance, for skin burns over 60-70% of the body surface or in the cornea total destruction of the limbal corneal epithelium. So in this case you have no stem cell to stimulate and therefore you have to replace the entire epithelium. In this case you do need maintenance of the stem cell in culture because you need to have transplantation and graft of the cultivated stem cells in order to regenerate the entire epithelium. Obviously this is mandatory also for the gene therapy because in this case you have to replace the genetic diseased skin with autologous stem cells that have been genetically corrected. So it’s two different types of approach.

What are the genetic applications?

For the corneal epithelium we have lots of experience, we have done more than 250 patients or almost 300; we have ten to fifteen years follow-up on these patients so it’s a solid, established cell therapy. For the gene therapy we are just in the phase I clinical trial and we were able to demonstrate as a proof of principle that genetically modifying epidermal stem cells, autologous obviously, can be engrafted and can generate a good epidermis in patients, as I said, with epidermolysis bullosa, it’s a devastating skin disease. But it’s a phase I/phase II clinical trial so we need much more basic work in patients to show this can be an area of therapy. At this stage it’s not that easy because the regulations, the new regulations, for clinical trials both in cell therapy and in gene therapy are very strict and very mandatory. So you need lots of time, lots of money to implement clinical trials, it’s not like it was twenty years ago.