1. — Dental and tissue engineering researchers at Tufts University School of Dental Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts have harnessed the pluripotency of human embryonic stem cells (hESC) to generate complex, multilayer tissues that mimic human skin and the oral mucosa (the moist tissue that lines the inside of the mouth). The proof-of-concept study is published online in advance of print in Tissue Engineering Part A.
Using a combination of chemical nutrients and specialized surfaces for cell attachment, an hES cell line (H9) was directed to form two distinct specialized cell populations. The first population forms the surface layer (ectodermal, the precursor to epithelial tissue), while the second is found beneath the surface layer (mesenchymal).
Following the isolation and characterization of these cell populations, the researchers incorporated them into an engineered, three-dimensional tissue system where they were grown at an air-liquid interface to mimic their growth environment in the oral cavity. Within two weeks, tissues developed that were similar in structure to those constructed using mature cells derived from newborn skin, which are the current gold standard for tissue fabrication.
“These engineered tissues are remarkably similar to their human counterparts and can be used to address major concerns facing the field of stem cell biology that are related to their clinical use. We can now use these engineered tissues as ’tissue surrogates’ to begin to predict how stable and safe hESC-derived cells will be after therapeutic transplantation. Our goal is to produce functional tissues to treat oral and skin conditions, like the early stages of cancer and inflammatory disease, as well as to accelerate the healing of recalcitrant wounds,” said Garlick.
The results demonstrate for the first time that it is possible for adult tissue to develop into the full range of the body’s different cell types, in a manner similar to embryonic stem cells.
If the technique were to be repeated in humans, it could offer the prospect of a limitless supply of an individual’s own stem cells and be used to treat conditions such as Parkinson’s disease, paralysis and diabetes.
In the Chinese study, details of which were published online yesterday in the journal Nature, skin cells were taken from adult mice. These were then reprogrammed to turn them into a versatile, embryo-like state by modifying four key genes using viruses.
Previously, iPS cells have been shown to be capable of turning into different cell types in culture, such as blood, skin and muscle cells. But until now they have not passed the ultimate test of versatility — that of being turned into a living creature.
In order to create a suitable environment for the stem cells to grow into an embryo, they were injected into a blastocyte — a group of cells that can only become placental tissue. This was implanted into an adult female mouse, which went on to give birth to pups that were clones of the mouse from which the skin cell had been taken.
While mice and other mammals — but not human beings — have been cloned before, this has always involved inserting DNA from an adult cell into an empty egg.
“This paper demonstrates that mouse cells can be reprogrammed to reacquire the characteristics of genuine embryonic stem cells — namely the ability to form an entire mouse,” said Professor Ernst Wolvetang, a stem-cell specialist at the Australian Institute of Bioengineering and Nanotechnology.
In total, 27 mice have been created using the new technique. They have since gone on to produce about 200 offspring, which, in turn, have also reproduced. The majority of the mice showed no obvious health problems.