Scientists at the universities of Edinburgh and Toronto have found a way to achieve the same feat without using viruses, making so-called induced pluripotent stem (iPS) cell therapies a realistic prospect for the first time.
In 2007, researchers in Japan and America announced they had turned adult skin cells into stem cells by injecting them with a virus carrying four extra genes. Because the virus could accidentally switch on cancer genes, the cells would not be safe enough to use in patients.
In two papers published in the journal Nature, Keisuke Kaji in Edinburgh and Andras Nagy in Toronto, describe how they reprogrammed cells using a safer technique called electroporation. This allowed the scientists to do away with viruses and ferry genes into the cells through pores. Once the genes had done their job, the scientists removed them, leaving the cells healthy and intact.
Tests on stem cells made from human and mouse cells showed they behaved in the same as embryonic stem cells.
Stem cells can thrive in segments of well-vascularized tissue temporarily removed from laboratory animals, say researchers at the Stanford University School of Medicine. Once the cells have nestled into the tissue’s nooks and crannies, the so-called “bioscaffold” can then be seamlessly reconnected to the animal’s circulatory system. This is an incredible opportunity to bulk-deliver cells that don’t just die.
A new technique neatly sidesteps a fundamental stumbling block in tissue engineering: the inability to generate solid organs from stem cells in the absence of a reliable supply of blood to the interior of the developing structure.
Gurtner and his colleagues removed microcirculatory beds about the size of a half-dollar coin from the groin of laboratory rats and attached the ends of the two main blood vessels to a modified piece of equipment called a bioreactor designed to keep livers and kidneys healthy outside the body. The modified bioreactor pumps an oxygenated soup of nutrients into one vessel and recovers it from the other; Gurtner referred to it as a “kind of life support, or cardiopulmonary bypass, machine for tissue.”
The scientists showed that, once the appropriate blood pressure and nutrient balance was achieved, the bioreactor could keep the tissue healthy enough for reimplantation into a second, genetically identical animal for up to 24 hours. In many cases, the tissue became nearly indistinguishable from surrounding skin within 28 days of transplant, although the success rate of the procedure decreased as time spent on the bioreactor increased. In contrast, control tissue not connected to the bioreactor after removal died within six hours of transplantation.
The team then used the bioreactor to pump multipotent stem cells from a variety of sources, including bone marrow and fat tissue, through the tissue. Unlike embryonic stem cells, which can become any type of cell in the body, multipotent cells are more restricted in their potential. The researchers found that the cells could migrate out of the vascular spaces and into the surrounding tissue. Once there, they set up shop and began to form colonies. Unlike stem cells injected directly into the tissue, the stem cells that had been seeded into the tissue continued to thrive even eight weeks after reimplantation.
Members of Gurtner’s team are now trying to use the technique to deliver Factor VIII and Factor IX — crucial blood-clotting components that are missing in people with hemophilia. The researchers concede, however, that much remains to be done before the technique could be used to generate whole organs. Indeed, Gurtner readily agrees that other methods might be developed that could be more effective. But for now, they’ve overcome a major hurdle in tissue engineering.