Researchers have developed a quick and easy method, involving just two key ingredients, for the conversion of skin cells into white blood cells. The team believes that the technique could eventually be used to supply patients with personalized immune cells capable of attacking diseased cells or even tumors. The work has been published in Stem Cells.
Induced pluripotent stem cells—adult cells that have been reprogrammed into an embryonic-like state—are attractive in the field of regenerative medicine because of their ability to differentiate into virtually any type of cell found in the body. While research on these cells looks promising, there are several obstacles that need to be overcome before they can be therapeutically useful. Namely, they have a tendency to form tumors and thus have safety issues, and they often fail to successfully engraft into organs or bone marrow. The process of producing, characterizing and differentiating these cells is also lengthy, taking several months from start to finish. But researchers may have now found a much more efficient mechanism to produce white blood cells from adult cells.
The new process, called indirect lineage conversion, takes just two weeks to produce a type of white blood cell from skin cells. White blood cells are immune cells that are responsible for a variety of jobs in the body, such as defense against infection and clearance of abnormal cells before they become cancerous.
Unlike the process of producing induced pluripotent stem cells, the new technique only turns back the clock part of the way. To do this, Salk Institute researchers overexpressed a molecule called SOX2 in human skin cells. The gene that produces this protein was previously found to be upregulated in mice during reconstitution of the hematopoietic system (the system involved in the production of blood).
SOX2 basically induced cellular memory loss, causing the skin cells to forget their previous identity and become malleable. Then, they used a short, non-coding RNA molecule called a microRNA to commit the cells to becoming an immature hematopoietic-like progenitor cell. When they transplanted these cells into mice, they successfully matured into white blood cells and did not cause tumors.
The researchers are now carrying out further safety and transplantation studies in anticipation of preclinical trials.
“It is fair to say that the promise of stem cell transplantation is now closer to realization,” study co-author Ignacio Sancho-Martinez said in a news release.