Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
The goal is to one day be able to propose this unlimited resource of cells as an alternative treatment in particular for victims of third degree burns and patients with genetic diseases affecting the skin. These studies were financed in particular by Telethon donations.
Cell therapy has radically changed the life of serious burn victims. For more than two decades, physicians have used cell culture techniques in order to obtain a sufficiently large area of skin to reconstruct the destroyed epidermis from a small sample harvested from the patients themselves.
Although this type of graft has been used with success, one of its limits is the time required (three weeks) to produce a sufficient amount of epidermis to cover the affected areas, leaving the patient unprotected during this interval. For a few years, research has led to the development of skin substitutes that help protect patients during the period before grafting. However, these technological means do not rule out the risk of immune rejection and transmission of disease.
Rapid access to an unlimited number of cells capable of yielding a well-formed epidermis, perfectly controlled in the laboratory before use, would therefore be the ideal solution to the problems posed by existing techniques. For these reasons the I-STEM researchers attempted to reconstruct a whole epidermis using human embryonic stem cells.
Human embryonic stem cells (hES) have two fundamental characteristics: a capacity for unlimited proliferation and pluripotency i.e. the capacity to differentiate into all the cell types in the human body.
The first objective of the team was to obtain skin stem cells (keratinocytes) similar to those naturally present in the human epidermis from hES cells. Keratinocytes, permit the constant renewal of the skin.
Once this stage was achieved, the second objective of the researchers consisted in finalising strategies to isolate keratinocyte stem cells in order to test their capacity to reconstitute a functional epidermis firstly in vitro - then 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" pointed out Christine Baldeschi.
The transformation of hES cells into epidermal cells was made possible by a combination of cell biology and pharmacological approaches . A "cell niche" was first created around the ES cells to guide them towards an epidermal destiny and an appropriate pharmacological agent was then added to the culture medium. The researchers decided to maintain this treatment for the 40 days that is normally required for an embryo to form its epidermis. By applying this concept of respecting chronobiology, the hES cells engaged in this differentiation process acquired first the markers of a simple epithelium and then finally those of keratinocytes. A population of cells presenting all the characteristic marker of adult keratinocytes was isolated and then amplified. It is without doubt by maintaining this treatment for 40 days that the I-STEM team succeeded where many others had failed.