Stem cell research has reached a new level of achievement. In late 2009 ScienceDaily reported that the first ever reconstruction of a whole epidermis from human embryonic stem cells was successful. The study was orchestrated by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), and published in the Lancet on November 21. The researchers’ goal? To finally recreate normal, functional skin.
The I-STEM studies, partially financed by donations from a telethon, produced skin that could hopefully be used as an aid to treatment for those suffering from genetic skin diseases and third-degree burns. Cell therapy has already changed the lives of patients suffering from severe burns. Doctors have used these cell culture procedures for over twenty years, so as to garner a large enough portion of skin to then reconstruct the parts that were destroyed from just a tiny sample harvested from the patients themselves. Skin grafts of this kind were always limited by the length of time needed (about three weeks) to harvest enough skin to completely cover the areas of the body that were damaged. During the three-week period while the new skin is grown, the patient’s damaged surface is left unprotected, leaving the patient vulnerable to infection. Research over the last few years has mitigated the problem, but current skin substitutes used to protect the patients during the interval before their skin grafts were applied still cannot protect against disease, and remain vulnerable to immune rejection.
Taking note of the limitations of the previous skin substitutes, the researchers concluded that the only solution was to obtain access to cells in limitless numbers, which would be able to yield a whole epidermis, and quickly. In order to be ideal for skin grafting, the cells would need to be controlled in the lab before they could be used. The I-STEM team took on the task of harvesting human embryonic stem cells and using them to recreate a normal human epidermis.
Researchers say that human embryonic stem cells (hES) are the only ones that can do the job. The reason? These cells have two basic characteristics: they can proliferate in unlimited quantities, and they are ‘pluripotent’, that is, they can form any cell type. Simply put, hES are not limited to certain cell types; they are the body’s blank slates, able to adapt to their surroundings. Because of this ability, they can be used anywhere, to recreate any skin. The team’s first goal was to acquire skin stem cells (keratinocytes, which allow for the constant renewal of skin) similar to the ones that exist in the human epidermis naturally. After the scientists completed this task, their next goal was to further develop methods that would allow them to isolate keratinocyte stem cells so that their capacity to reconstitute a functional epidermis could be fully tested. “It is these cells that interest us,” explained Christine Baldeschi, leader of the I-STEM team, “as they are the only cells capable of recreating all the layers of the human epidermis.”
Pharmacological approaches combined with cell biology allowed for the hES cells to transform into epidermal cells. What is known as a “cell niche” was first formed around the ES cells in order to guide them toward becoming epidermal. Then, a “pharmacological agent” was added to the medium. However, it was the 40 day culturing period that secured the experiment’s success. The scientists chose to harvest the culture for 40 days, the time needed for an embryo to form its epidermis.
After initial trials were successful, the team’s final goal was to reproduce the same results in mice. To do this, they collaborated with a Spanish team whose specialty in animal skin grafts would prove helpful. The results were positive. Twelve weeks after the transplant, the affected mice presented areas of completely functional adult human epidermis. Team director Marc Peschanski noted the breakthrough: “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.” Thanks to the I-STEM team, these treatments will have many uses in the future. Patients who could benefit from this development include those suffering from third degree burns, as well as patients with genodermatoses or ulcerations (known to complicate diabetes). “For more than twenty-five years we have known how to make epidermis with skin stem cells,” added Baldeschi, “and skin grafts are made in particular for victims of third degree burns. The keratinocytes obtained from human embryonic stem cells therefore have an immediate clinical application. We are now therefore seeking how, in concrete terms, to pass to man.”
Now the remaining battle lies on the frontlines of bioethics laws. This debate remains at the forefront of any hES research. French law permits only 28 research teams to work with embryonic stem cells, the I-STEM team among them. Their work means many patients may have new options in skin reconstruction and burn treatment.