Creating stem cells from adult cells – rather than using controversial embryonic material – is near the top of the list for stem cell research. So creating induced pluripotent stem cells (iPS – cells that can become almost any other kind of cell) from fat cells (yes, human fat cells, of which there is no short supply) would seem to be a good ticket. In fact, one of the researchers involved, Mark Kay of Stanford University School of Medicine (California, USA), was heard to say, “Why didn’t we think of this sooner?”
Of course, turning fat cells into stem cells is not simple. In the case of this research, it resulted from a fortunate combination of skills and knowledge.
The finding brings together disparate areas of Stanford research. Kay’s laboratory invented the minicircles several years ago in a quest to develop suitable gene therapy techniques. At the same time, Longaker was discovering the unusual prevalence and developmental flexibility of stem cells from human fat. Meanwhile, Wu was searching for ways to create patient-specific cell lines to study some of the common, yet devastating, heart problems he was seeing in the clinic.
“This is a great example of collaboration,” said Longaker. “This discovery represents research from four different departments: pediatrics, surgery, cardiology and radiology. We were all doing our own things, and it wasn’t until we focused on cross-applications of our research that we realized the potential.”
“About three years ago Mark gave a talk and I asked him if we could use minicircles for cardiac gene therapy,” said Wu. “And then it clicked for me, that we should also be able to use them for non-viral reprogramming of adult cells.”
Kay’s ‘minicircles’ are DNA elements arranged in microscopic rings. These can be injected into the body of a cell to look and work somewhat like the cell’s own plasmids (circular DNA molecules found outside of the cell nucleus). The minicircles then direct the cell’s RNA to produce DNA, RNA, or other proteins for therapeutic effect. This is a proven technique that has a great virtue in not using viruses to reprogram DNA/RNA (viruses being difficult to safely filter and control). However, the technique had not been used before to reprogram adult cells into stem cells.
The minicircles were applied to fat cells because Wu’s and Longaker’s research had shown this type of adult cell to have a good DNA configuration for reprogramming and was relatively easy to isolate.
The final experiments with minicircles and fat cells, done in vitro (in a Petri dish), showed that stem cells were created at the rate of about 0.005% of cells – a low rate compared to other techniques, but given the plenitude of fat cells, not a problem for production. The stem cells produced appear to have no differences from pluripotent cells from other sources.
As time will tell, if this method for producing stem cells is viable and scalable (can be done in large quantities), then it is indeed a major step toward making stem cells available for many kinds of diagnostic and therapeutic applications.