You can't get blood from a stone, but you may be able to get it from skin. Researchers have coaxed adult skin cells to morph into a variety of blood cells. The scientists transformed the cells into blood without first "reprogramming" them into cells that resemble embryonic stem cells, suggesting that this transformation might not be necessary for making replacement tissues.
Embryonic stem (ES) cells can potentially transform into any cell type in the body, but they carry a heavy load of ethical baggage. By inserting four genes or RNA sequences, researchers can reprogram adult cells, coercing them to "unspecialize" into induced pluripotent stem (iPS) cells with the talents of ES cells. Although scientists have spurred iPS and ES cells to develop into blood cells, both kinds of stem cells remain problematic. For one thing, researchers are worried about their potential to become cancerous. Another limitation, says stem cell biologist Mickie Bhatia of McMaster University in Hamilton, Canada, is that the resulting blood cells make little of the adult variety of hemoglobin, the body's oxygen-toting protein, suggesting that they haven't matured.
Bhatia and colleagues wondered whether it was necessary to convert adult cells into iPS cells. Perhaps partially reprogrammed cells would work. Although such cells wouldn't be able to make as many types of cells, they might yield blood.
The team used a harmless virus to insert the gene OCT4—one of the four genes originally needed to reprogram adult cells—into human skin cells known as fibroblasts. As the researchers report online today in Nature, the procedure turned back the developmental clock part of the way. Instead of morphing into iPS cells, the treated skin cells became more specialized blood-forming cells similar to those that normally reside in the bone marrow. With further coaxing, these progenitor cells spawned defensive cells such as neutrophils, basophils, and macrophages, which munch on bacteria and other invaders.
The team was also able to nudge the progenitors into becoming red blood cells that transport oxygen through the body. Unlike the blood cells derived from iPS cells or ES cells, the cells created by the researchers predominantly manufactured the adult version of hemoglobin, Bhatia says. "We believe that because we are starting with adult fibroblasts, we are making adult erythrocytes [red blood cells]."
The cells appear to be safe. When the team injected them into mice, they didn't induce abnormal growths called teratomas. And in the culture dish, the cells divided only a limited number of times, indicating that they hadn't become immortal like cancer cells.
The researchers also tested whether the blood progenitors could establish themselves in recipients by inserting them into mice. After 8 weeks, about one-fifth of the cells in the animals' bone marrow were human, suggesting that the transplants had made themselves at home in the rodents.
After further development, the technique could lead to a more efficient way to make new blood cells, Bhatia says. For example, researchers might be able to replace the faulty blood cells of leukemia patients with healthy cells derived from their own skin. Scientists could also cultivate and stockpile blood of different types, much like donated blood is stored today, he says.
However, the researchers still have some work to do, says stem cell biologist Thalia Papayannopoulou of the University of Washington, Seattle. She wants to see stronger evidence that the transplanted cells will establish themselves for the long term in recipients, a perennial problem for stem cells.
But molecular biologist Dean Tantin of the University of Utah School of Medicine in Salt Lake City is enthusiastic. Because the Bhatia group's cells weren't fully reprogrammed, most scientists would write them off as failures, he says. The researchers "used other people's dead ends and turned them into gold." He predicts that "a lot of people are going to jump on this."