Bioengineered Skin

Scientists at Universidad Carlos III de Madrid (UC3M -- Carlos III University) are participating in research to study how to make use of the potential for auto regeneration of stem skills from skin, in order to create, in the laboratory, a patient's entire cutaneous surface by means of a combination of biological engineering and tissue engineering techniques.

The ability to generate mice that can have part of their skin replaced with human skin allows in vivo studies to be carried out; these studies could not be carried out any other way, given that human volunteers cannot be used due to ethical considerations. (Credit: UC3M)

Skin is a tissue that naturally renews itself throughout our lives thanks to the existence of epidermic stem cells. "We have found that this regenerative potential can be preserved in vitro (in the laboratory) if the cells are joined and become part of generated skin using tissue bioengineering techniques," explains Marcela del Río, of UC3M's Bioengineering. The research group in which she participates, made up of scientists from the UC3M, from CIEMAT (the Center for Energy, Environmental and Technological Research) and CIBERER (the Center for Biomedical Research in the Rare Disease Network) of the Carlos III Health Institute, has been working with this type of adult stem cells for years, with the objective of using them to regenerate patients' skin.

The researchers have already been able to join together these epidermic stem cells into skin created by means of bioengineering, and they have observed that the cells preserve the regenerative potential that they normally have in our skin. That is, using a small biopsy from a specific patient, they can generate almost the entire cutaneous surface of that individual in the lab. "The regenerative capacity of epidermic stem cells in these conditions is overwhelming, and it leads to the possibility of using these cells as a target for even more complex protocols, such as gene therapy," indicates Marcela del Río, who is a professor in the new Biomedical Engineering degree program at this Madrid university.

Patches of healthy skin

In fact, these researchers have already demonstrated, at the pre-clinical level, that it is possible to isolate epidermic stem cells from patients with different genetic skin diseases, cultivate them and, using molecular engineering as a first step, incorporate the therapeutic genes into each patient's genome to take the place of the one that the patient does not have or that functions abnormally. Afterwards, in the second step, the stem cells would be assembled into patches ready to be transplanted onto the patients.

In recent studies, researchers have isolated stem cells from patients suffering from Netherton syndrome, a genetic illness characterized by an excessive peeling of the skin that leads to a loss of the barrier function of the skin, which inhibits the loss of fluids so that we do not become dehydrated, or which stops pathogens that can cause infections from entering our bodies. These patients have a neonatal mortality rate of between 10 and 15 percent; the molecular basis of this pathology lies in a mutation of one gene, known as SPINK-5.

This gene inhibits the production of a protein that controls the process of skin shedding, ensuring that it occurs correctly. "What we did in this case -- explains Marcela del Río -- was to transfer a normal SPINK-5 gene to a patient's stem cells and later use these cells to generate skin that could be transplanted to experimental models, such as mice."

The results, which were recently published in the Journal of Investigative Dermatology, were that human skin that was regenerated in these immunodeficient mice showed a completely normal peeling process, so that epidermic structure and function were reestablished. "These pre-clinical studies could be transferred to clinical practice in the medium term, and could become a therapeutic strategy for patients who might otherwise have no treatment available to them," concludes the researcher.

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