Nature Communications reports that researchers at the Department of Biosystems Science and Engineering at ETH Zurich in Switzerland have succeeded in genetically reprogramming adipose stem cells into functional, insulin-producing beta cells.
The team of biotechnologists, led by Professor Martin Fussenegger, extracted fat cells from a 50-year-old study subject and applied so-called “genetic software” to convert them into mature beta cells, similar to the cells that produce insulin in the pancreas.
The genetic software used by the researchers consisted of a complex network of synthetic genes, designed to produce the growth factors that are the key to cell maturation. Ngn3, MafA, and Pdx1 are growth factors whose concentrations vary during cell differentiation, rising and falling in complex patterns. The Basel-based team of researchers succeeded in replicating the natural cell maturation process by precisely controlling the timing and quantity of these growth factors.
The use of a synthetic gene network to reprogram fat cells into beta cells is a genetic engineering feat previously considered impossible. Until now, scientists have added chemicals and proteins with pipettes to induce stem cells to differentiate, a process that is both inefficient and impractical to scale up. In contrast, the new process, Fussenegger states, can transform 75 percent of adipose stem cells into pancreatic beta cells.
The genetically engineered beta cells are similar in appearance to their natural counterparts, displaying the characteristic dark granules that store insulin. The artificially produced beta cells also function similarly in response to glucose, but are not able to produce the same large quantities of insulin that natural beta cells can, Fussenegger admits.
What is most meaningful about the method, according to the researchers, is the ability to reproduce the entire cell maturation process from undifferentiated stem cells to fully functional beta cells. In the future, this new technique may allow diabetics to receive implants of functioning beta cells derived from their own fatty tissue. Until now, transplantation of beta cells has been similar to any other organ or tissue transplant, requiring the recipient’s immune system to be suppressed to prevent rejection of the “foreign” tissue.
Beta cells derived from the patient’s endogenous tissue can potentially revolutionize diabetes treatment. Although the researchers have been successful in culturing the beta cells and confirming their functionality in the laboratory, these artificial cells are yet to be implanted into a patient with diabetes. The research has, however, conclusively proven that it is possible to complete the process of stem cell differentiation from beginning to end with genetic programming. Down the line, the technique can further be extended to produce other cell lines. Meanwhile, the good news is that the overabundant fat in love handles can finally be put to some good use as a source of stem cell harvesting.