A study in this week’s edition of The Lancet reports that the use of human embryonic stem-cells (hESCs) is a promising alternative for producing temporary skin substitutes for patients awaiting skin grafts after, for example, serious burn injuries. The article is the work of Dr Christine Baldeschi, INSERM and Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, Evry Cedex, France, and colleagues.

For more than two decades, patients with serious burns have benefited from cell therapy to help them recover from their injuries. In this therapy, the patient’s own skin cells (keratinocytes) are taken. Then more are grown in the laboratory and used to replace the damaged skin. But the major disadvantage is that there is a three week period needed to grow enough cells. This puts the patients at risk of dehydration and infection. Decellularised skin from deceased persons can be used to cover wounds during this period. However, availability is limited and the tissue is often rejected by the host. To overcome the problem of accessibility, there has been active search and development for inert synthetic and biosynthetic matrices. Presently however, these substitutes have not replaced skin from deceased persons in large burns since they increase the risks of rapid graft rejection and disease transmission. This is due to the fact that they contain bovine collagen and adult allogenic skin cells.

In this research, the hESC were seeded on feeder cells using a pharmacological treatment over forty days. This treatment drives hESCs towards becoming keratinocytes linage. This is done by following biological steps that lead to epidermis formation during embryonic development. The team were capable to generate a population of cells that presented the characteristics of keratinocytes. Once placed on an artificial matrix, the cells were able to form a layer of skin. Just twelve weeks after grafting onto five mice, the skin layer derived from the hESCs had a structure similar to human skin.

The authors explain: “We have shown that keratinocytes can be derived from hESCs… Growing human epidermis from hESCs could have clinical relevance as an unlimited resource for temporary skin replacement in patients with large burns awaiting autologous grafts.”

They include that future research should assess whether or not this technology could extend the time needed to grow enough cells for a permanent graft, or if keratinocyte hESCs could be used for a permanent graft in cases where a permanent graft using the patients’ own keratinocytes is not possible.

In an associated comment, Dr Holger Schlüter and Dr Pritinder Kaur, Epithelial Stem Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia, remark: “This report takes research into regenerative skin stem cells to the next level…This finding suggests that keratinocyte allografts derived from hESC keratinocytes could be transplanted onto burnt patients awaiting skin grafts with a reduced risk of rejection.”

“Human embryonic stem-cell derivatives for full reconstruction of the pluristratified epidermis: a preclinical study”
Hind Guenou, Xavier Nissan, Fernando Larcher, Jessica Feteira, Gilles Lemaitre, Manoubia Saidani, Marcela Del Rio, Christine C Barrault, François-Xavier Bernard, Marc Peschanski, Christine Baldeschi, Gilles Waksman
Lancet 2009; 374: 1745-53
The Lancet

Written by Stephanie Brunner (B.A.)