Getting Genes into Stem Cells Without Viruses

Genetic engineering of cells and, in particular, of stem cells has the ability to adjust the functional capacities of cells. Unfortunately, genetically engineering cells requires the use of viruses that introduce genes into cells and, by doing so, produce mutations in cells.

However, there are new ways to put genes into cells without the use of viruses. By surrounding DNA that encodes the genes you want to put into cells with positively-charged lipids, you have made a structure called a liposome. Liposomes can fuse with the membranes of cells and deliver the genes to cells without viruses that can cause mutations.

A paper that has appeared in the journal Stem Cells and Development examined the use of liposomes to introduce genes into blood cell-making stem cells (HSCs). They used commercially-available systems to transfer genes into these stem cells, but they found that their own lab-designed system did a better job than the commercially-available systems.

The lead author of this paper is Hilal Gul-Uludag and the senior author is Jie Chen from the University of Alberta in Edmonton, Alberta, Canada. In this paper, Chen’s research group isolated blood cell-making stem cells from umbilical cord blood. Then they used liposomes to insert the CXCR4 gene. The CXCR4 gene encodes a receptor for “stromal cell-derived factor-1alpha” (SDF-1alpha). When cells bind to SDF-1alpha, they move towards the source of SDF-1alpha.

Interestingly, one of the best sources of SDF-1alpha is the bone marrow. If HSCs could be engineered to make CXCR4, then they would readily move into the bone marrow. This means that implanted HSCs would only need to be introduced into the peripheral blood and not into the bone. This would increase the efficiency of bone marrow or umbilical cord transplants.

Chen’s group showed the feasibility of such experiments, and that these treatments are not toxic in any way to the HSCs. Thus, such a strategy could potentially increase the efficiency of bone marrow and umbilical cord blood transplantation.