This story begins with an insight: The cells of a vascular system (veins, arteries, capillaries) – called endothelial cells – do more than make up the tissue that transports blood; they also play a role in maintaining blood (hematopoietic) stem cells by producing novel stem-cell-growth factors. A research team at the Ansary Stem Cell Institute at Weill Cornell Medical Collage (New York, USA) discovered that by culturing stem cells together with adult endothelial cells, the stem cells would continue propagating and remain alive far longer than with any other technique – weeks, instead of days. This opens a door to producing stem cells in quantity.
The use of endothelial cells built on work by Dr. Shahin Rafii, which produced genetically modified endothelial cells so they would stay in a long-term survival state. (Otherwise endothelial cells require difficult maintenance with specific growth factors to keep them alive.) The genetic modification inserted a gene from a recently discovered adenovirus, one that does not promote cancer forming transformation of human cells – an obviously important qualification.
“This study will have a major impact on the treatment of any blood-related disorder that requires a stem cell transplant,” says the study’s senior author, Dr. Shahin Rafii, the Arthur B. Belfer Professor in Genetic Medicine, co-director of the Ansary Stem Cell Institute and a Howard Hughes Medical Institute Investigator, at Weill Cornell Medical College. Currently, stem cells derived from bone marrow or umbilical cord blood are used to treat patients who require bone marrow transplants. Most stem cell transplants are successful, but because of the shortage of genetically matched bone marrow and umbilical cord blood cells, many patients cannot benefit from the procedure.
“Over the last few decades, substantial funding has been spent to develop platforms to expand adult stem cell cultures, but these efforts have never been able to coax an authentic adult stem cell to self-renew beyond a few days,” continues Dr. Rafii. “Most stem cells, even in the presence of multiple growth factors, serum, and support from generic non-endothelial stromal cells, die after a few days. Now, employing our endothelial stem cell co-cultures, we can propagate bona fide adult stem cells in the absence of external factors and serum beyond 21 days with an expansion index of more than 400-fold.”
This study also shed new light on the functions of endothelial cells, well beyond their fundamental use as the basic tissue of the vascular system, and even beyond their (now demonstrated) role in production of adult blood stem cells. It appears that endothelial cells contribute control factors for the production of a number of adult (that is, differentiated) stem cells for other organs such as the brain, liver, and lungs.
The PR announcement for this study is almost breathless from uttering superlatives like ‘breakthrough’ and ‘innovative.’ Probably so, but it also mentions that the results are pending verification – that is, reproduction of the experiments and results by other scientists. That would also include unexpected behaviors like side effects that could result from producing adult stem cells in this fashion. Nevertheless, this seems to be an important step in the direction of producing sufficient quantities of non-embryonic, long-lasting stem cells for medical and laboratory purposes.