Friday November 20 2009
Human embryonic stem cells
“Stem cells could create new skin to help burn victims,” BBC News reported. It said that French researchers have duplicated the biological steps that occur during skin formation in embryos. This could potentially provide an unlimited source of temporary skin replacements for burn victims while they wait for grafts from their own skin.
The study in mice behind this report used human embryonic stem cells to make keratinocytes (the most common cell types in the skin). These cultured cells were used to create skin equivalents, which grew successfully when they were grafted onto the backs of mice.
This well-conducted research has potentially developed a successful method of culturing tissue in the laboratory that resembles human skin. Only human trials of the technology will show whether such grafts will be accepted (i.e. not rejected by human patients) as permanent transplants or can provide a temporary skin replacement before grafting.
Where did the story come from?
The research was carried out by Dr Hind Guenou and colleagues from the Institute for Stem Cell Therapy and Exploration of Monogenic disease, and BIOalternatives SAS in France along with colleagues in Madrid. The research was funded by the Institut National de la Santé et de la Recherche Médicale, University Evry Val d’Essonne, Association Française contre les Myopathies, Fondation René Touraine, and Genopole. The authors declare that they have no conflicts of interest and say that the funders had no role in the study’s design, analysis or write-up.
The research was published in the peer-reviewed medical journal the Lancet.
BBC News has covered this research in a balanced way, pointing out that this was animal research and that human studies will follow.
What kind of research was this?
This well-conducted research involved laboratory and animal research which investigated whether epidermal stem cells could be cultured in the laboratory and used in skin grafts.
What did the research involve?
Burn patients are often treated using autologous skin grafts. These involve a section of healthy skin being removed from another part of the body to harvest the patient’s own skin cells for culture. A graft for the burn site is produced from this culture. There is a delay of about three weeks between the harvesting of the skin and the graft to allow the cells to grow. During this time, the patient is at risk of dehydration and infection.
Having a ready source of skin cells for temporary grafts while patients are waiting for their autologous grafts would improve the outcome of treatment. With this in mind, the researchers investigated whether keratinocytes (the major cell constituent of the outer layer of the skin, or epidermis) could be derived from human embryonic stem cells.
The researchers began by culturing embryonic stem cells in a specialised medium that encourages cell differentiation (the process whereby cells become specialised). Embryonic stem cells can renew themselves and also have the potential to develop into any type of specialised cell.
Cultures of human embryonic stem cells were then grown on a framework made of fibroblast cells and collagen (a fibrous protein that can form a mesh-like structure) made by fibroblasts. Fibroblasts are the cells that form the underlying structure of tissues and are involved in healing.
The stem cells were manipulated so that they developed into epidermal cells, and monitored throughout their specialisation process to make sure the cells were developing into skin cells. The researchers named the cells “keratinocytes derived from human embryonic stem cells” (K-hESCs).
After several rounds of subculturing and replication, the cells could be frozen and used in further experiments. “Bioengineered skin equivalents” were then created by growing the K-hESCs on an artificial matrix. These were then grafted onto the backs of five six-week-old immunodeficient female mice. After 10 to 12 weeks, samples were taken from the implants for analysis.
What were the basic results?
The researchers confirmed that the embryonic stem cells differentiated into keratinocytes, which could be grown in culture medium and which replicated well. These derived skin cells were structurally and functionally similar to normal skin cells in that they could be grown on an artificial matrix using classic techniques.
After 12 weeks of growth on immunodeficient mice, the grafted epidermis had developed into a structure that was consistent with mature human skin.
How did the researchers interpret the results?
The researchers concluded that their findings build on previous research and show that K-hESCs can develop into a multi-layer epithelium. This epithelium resembles normal human skin both in cell cultures (in vitro) and following grafting onto live animals (in vivo).
They say that growing human skin from human embryonic stem cells could provide an unlimited resource for temporary skin replacement in patients with large burns who are waiting for autologous skin grafts.
If it can be demonstrated that it works in humans, this technology could improve outcomes for burns patients. The researchers report that the first human trial is currently underway.
At present, skin from deceased donors is used to treat burns patients while they wait for their own skin transplant, but there are often problems with rejection. The researchers highlight several potential benefits of an epidermis reconstructed using K-hESCs, including:
- The potential to make large quantities as it can be developed fully in the laboratory. The researchers say that industrialisation of the manufacturing process would reduce the risk of infection.
- Less chance of rejection by the host because K-hESCs are in an early developmental stage and, therefore, don’t produce much antigen (the substance which causes an immune response).
It is important to note that, at present, the researchers are only investigating this technology for providing temporary grafts. They say that whether it can be used for permanent grafts for patients who can’t use their own cells needs further investigation. They say that for temporary use, the grafts would only be used for the three-week period while the patients’ permanent graft is grown.
This is a good study and the findings are exciting in this field, but only human research will tell whether it will have a wider application in the treatment of burns patients.