French researchers have become the first to report generating a whole, multicellular and fully functional epidermis from human embryonic stem cells (hESCs).
The scientists, at INSERM’s I-STEM (Institute for Stem Cell Therapy and Exploration of Monogenic Diseases) Institute, claim the achievement will have major applications in the future treatment of patients with third-degree burns and skin diseases such as genodermatoses diabetic ulcers. Their work is reported in The Lancet, in a paper titled, “Human embryonic stem-cell derivatives for full reconstruction of the pluristratified epidermis: a preclinical study.” The I-STEM unit is one of only 28 teams in France licensed to conduct research on hESCs.
Christine Baldeschi, Ph.D., and colleagues first generated keratinocyte stem cells from hESCs. The next step was to isolate these cells and confirm that they could develop into the full and complete range of epidermal cells both in vitro and in vivo. “It is these cells that interest us as they are the only cells capable of recreating all the layers of the human epidermis,” Dr. Baldeschi pointed out.
The transformation of hESCs into keratinocytes was achieved through a combination of cell biology and pharmacology. Appropriately isolated and “fed” hESC cells were treated pharmacologically for 40 days, the time required for an embryo to form its epidermis. The scientists maintain it is this prolonged treatment that resulted in the generation of a population of cells that had all the characteristic markers of adult keratinocytes.
Further in vitro work then confirmed these hESC-derived keratinocytes could generate a functional epidermis in vitro. The resulting tissue demonstrated all the features, including self-renewal, stratification, and final differentiation, necessary for a fully functioning epidermis.
Collaborating with a research team in Spain, the researchers then tested the keratinocyte grafts in immunocompromised mice to negate the potential for graft rejection. Twelve weeks after graft transplantation, the mice demonstrated localized areas of completely normal and functional adult human epidermis that comprised all the skin cell types.
The authors suggest the hESC keratinocyte technology could be developed to provide temporary skin substitutes for patients awaiting autologous grafts. “Our team is currently the only one to have succeeded in finalizing a protocol making it possible to transform human embryonic stem cells into a pure and homogeneous population of keratinocytes able to reconstitute a whole epidermis both in vitro and in vivo,” claims I-STEM director, Marc Pschanski, M.D., co-author of The Lancet paper.