In a new study scientists have successfully transformed human skin cells into blood without first being sent through a primordial, stem-cell-like state. The findings were published online in the journal Nature. Earlier work has shown that fibroblast cells from mouse skin, treated with the right cocktail of chemicals, can be transformed into neurons and heart muscle. This is a first with human cells.
Ian Wilmut, an embryologist and director of the MRC Centre for Regenerative Medicine in Edinburgh, UK said, “It takes us a step along the line to believing that you can produce anything from almost anything.” He added that such “direct conversions” also offer a potentially safer, simpler tool for creating patient-specific cell therapies than is promised by adult cells reprogrammed to become stem cells (known as induced pluripotent stem cells, or iPS cells).
Mickie Bhatia, a stem-cell researcher at McMaster University in Hamilton, Canada, and his colleagues preferred to use blood progenitors from skin cells because red blood cells created from stem cells do not make the adult form of hemoglobin. “Those cells, because they think they're embryonic, make embryonic and fetal blood,” he explained. The team collected skin fibroblasts from several volunteers. They infected the cells with a virus that inserted the gene OCT4, and then grew them in a soup of immune-stimulating proteins called cytokines. The progenitors produced all three classes of blood cells (white blood cells, red blood cells and platelets) all of which seemed to function as they should, according to a battery of experiments. The red blood cells made adult hemoglobin, not the fetal form.
The next step, according to Bhatia would be transplanting the cells into humans. He said, “The clinical side is going to be a lot of work… At least from our estimation, this is the most encouraging result we’ve seen for using blood cells for cell-replacement therapy.”
Wilmut adds that since these progenitor cells bypass pluripotency, there is little risk of them forming tumors when implanted into patients.
Deepak Srivastava, a developmental biologist and director of the Gladstone Institute of Cardiovascular Disease in San Francisco, California had led a team earlier with the mouse fibroblasts. On this latest finding he said that directly converted cells could also offer simpler treatments than iPS cells: the fibroblasts that surround the heart could be transformed into new heart muscle using a stent that delivers drugs to reprogram the cells.
However Wilmut warns that these converted cells cannot easily multiply in the lab, so producing the large quantities needed for applications such as screening drugs could prove tough.
Cynthia Dunbar, head of the molecular hematopoiesis section of the National Heart, Lung and Blood Institute of the National Institutes of Health in the United States, said she was eager to try out the Canadian team’s approach. She said, “I think there are exciting aspects in terms of this potentially being a much safer approach than going back through embryonic stem cells…I work for the US federal government, and whether or not we can work with embryonic stem cells is up in the air… I’m very excited to try this.”
Clinical trials are to begin as early as 2012. Leukemia patients are likely to be the first to receive transfusions of perfectly matched blood generated from their own skin. The research was funded by the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, the Stem Cell Network and the Ontario Ministry of Research and Innovation.
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