French researchers make new skin
A team of French scientists has managed to recreate an entire epidermis from human embryonic stem cells. This world first represents a lot of hope for the treatment of third-degree burn victims, diabetics and patients suffering from genetic diseases affecting the skin.
Reconstructing human epidermis was no ordinary endeavour. It proved both particularly difficult and quite spectacular. Difficult because “skin is an organ made up of several cells organised together,” explains Marc Peschanski, the director of I-Stem, the stem cell institute based in Evry in the Paris region where this feat was achieved. Spectacular because embryonic stem cells (from excess embryos donated to science following in-vitro fertilisation) have “magical” powers. They have the capacity for unlimited proliferation, and also the capacity to differentiate into all the cell types in the human body.
The first stage of the researchers’ work was to obtain skin stem cells (keratinocytes) similar to those naturally present in human epidermis. The transformation of stem cells into epidermal cells was carried out in a cell niche, a culture bath, for forty days (the time it normally takes for an embryo to form its epidermis).
After the in-vitro phase came the in-vivo phase, which involved grafting the cells onto mice. Twelve weeks afterwards the mice presented a fully functional adult human epidermis with all its components!
According to the technical timetable drawn up by the scientists, human clinical trials should begin within two years. Eventually a skin bank might be set up which could save many human lives. Third-degree burn victims, for example, are currently treated by self-grafting; but in order for the skin the size of a postage stamp that is taken to become a square metre of epidermis, it is necessary to wait for three weeks. During this time the patient suffers from dehydration and infections that often prove fatal. “The skin bank would provide an immediately available reserve,” stresses Marc Peschanski.
The breakthrough achieved by I-Stem also represents great hopes for children suffering from painful genetic diseases affecting the epidermis, such as epidermolysis bullosa, as well as for diabetics who suffer from skin ulcers.
In France, research on embryonic stem cells is still prohibited, except for certain exemptions (from which I-Stem obviously benefits). The publication of the results on the making of epidermis by the leading British scientific journal The Lancet, may well give rise to some reflection, notably on the part of members of parliament, in relation to the planned review of the law on bioethics.
Since 1981, when embryonic stem cells were identified in the mouse and 1998, when human stem cells were properly identified, a lot of work has been required to assemble the resources and get research projects off the ground. The creation of epidermis falls within the framework of studies on genetic diseases of the skin, but the increasing pace of discoveries means that other possibilities can be envisaged, notably in the treatment of leukaemia, certain cancers, heart attacks, myopathies and brain injuries. Several years ago, Marc Peschanski and his teams themselves carried out the world’s first graft of foetal neurons onto patients suffering from Huntington’s Chorea.
I-Stem is today a rapidly expanding laboratory which has cutting-edge technology such as the robot for high throughput screening in its 1800-sq-m premises. A partner of the AFM, the French Association against Myopathies, which pays it 3 million euros per year, it also receives significant support from the French public authorities and the European Union. New teams have joined it, such as that of Michel Pucéat, a specialist in embryonic stem cells and in cardiac differentiation. The laboratory, which has already more than doubled its staff, will employ around a hundred people in 2010.
But “no development is possible if you remain isolated internationally,” insists Marc Peschanski. For the final stage of creating the skin, the mouse stage, the French laboratory joined forces with Spanish researchers, specialising in grafts on animals. The manager of I-Stem, an instigator, among others, of Nectar – the Network for European CNS Transplantation and Restoration – points out: “We are closely connected to a community of European teams and we have also developed a special partnership with Japan, the leader in genetic reprogramming of adult cells to make them resemble embryonic stem cells.” This research requires specialists in all fields... and all countries, to come together.