The work, as detailed in the journal Stem Cells, shows that only a bit of creative manipulation is needed to turn skin cells into human white blood cells.
"The process is quick and safe in mice," says senior author Juan Carlos Izpisua Belmonte, holder of Salk's Roger Guillemin Chair. "It circumvents long-standing obstacles that have plagued the reprogramming of human cells for therapeutic and regenerative purposes."
Those problems includes the long time—at least two months—and tedious laboratory work it takes to produce, characterize and differentiate induced pluripotent stem (iPS) cells, a method commonly used to grow new types of cells. Blood cells derived from iPS cells also have other obstacles: an inability to engraft into organs or bone marrow and a likelihood of developing tumors.
The new method takes just two weeks, does not produce tumors, and engrafts well.
"We tell skin cells to forget what they are and become what we tell them to be—in this case, white blood cells," says one of the first authors and Salk researcher Ignacio Sancho-Martinez. "Only two biological molecules are needed to induce such cellular memory loss and to direct a new cell fate."
Belmonte's team developed the faster technique (called indirect lineage conversion) and previously demonstrated that these approaches could be used to produce human vascular cells, the ones that line blood vessels. Rather than reversing cells all the way back to a stem cell state before prompting them to turn into something else, such as in the case of iPS cells, the researchers "rewind" skin cells just enough to instruct them to form the more than 200 cell types that constitute the human body.
The technique demonstrated in this study uses a molecule called SOX2 to become somewhat plastic—the stage of losing their "memory" of being a specific cell type. Then, researchers use a genetic factor called miRNA125b that tells the cells that they are actually white blood cells.
The researchers are now conducting toxicology studies and cell transplantation proof-of-concept studies in advance of potential preclinical and clinical studies.
"It is fair to say that the promise of stem cell transplantation is now closer to realization," Sancho-Martinez says.
Study co-authors include investigators from the Center of Regenerative Medicine in Barcelona, Spain, and the Centro de Investigacion Biomedica en Red de Enfermedades Raras in Madrid, Spain.
About the Salk Institute for Biological Studies:The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probes fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.
Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, MD, the Institute is an independent nonprofit organization and architectural landmark.
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