Blood Cells Reprogram into Embryonic State

When is a blood cell not a blood cell?  When scientists from John Hopkins turn it into a stem cell that looks and behaves as it did when it was part of a 6-day-old embryo. Elias Zambidis, M.D., Ph.D., Assistant Professor of Oncology and Pediatrics at the Johns Hopkins Institute for Cell Engineering and the Kimmel Cancer Center, has coaxed adult blood cells to become induced-pluripotent stem cells (iPS)–adult cells reprogrammed to an embryonic-like state, and bearing unprecedented efficiencies.

Zambidis says his team has managed to develop a “super efficient, virus-free” way to make iPS cells. Generally, out of hundreds of blood cells, only one or two might turn into iPS cells. Using Zambidis’ method, 50-60% of blood cells can be engineered into iPS cells.

Zambidis’ team also found a way around the use of viruses to convert the cells to a stem cell state. Traditionally, scientists have used viruses to deliver a package of genes to cells to turn on processes that convert the cells from one type (such as skin or blood) back to stem cell states. However, viruses used in this way can mutate genes and initiate cancers in newly transformed cells. To insert the genes without using a virus, Zambidis’ team uses plasmids, rings of DNA that replicate briefly inside cells and then degrade. The blood cells were also stimulated with their natural bone-marrow environment.

Here is how they did it. The Johns Hopkins team took cord blood cells, treated them with growth factors, and used plasmids to transfer four genes into them. They then delivered an electrical pulse to the cells, making tiny holes in the surface through which the plasmids could slip inside. Once inside, the plasmids triggered the cells to revert to a more primitive cell state. The team then grew some of the treated cells in a dish alone, and some together with irradiated bone-marrow cells.

When scientists compared the cells grown using the blood cell method with iPS cells grown from hair cells and from skin cells, they found that the most superior iPS cells came from blood stem cells treated with just four genes and cultured with the bone marrow cells. These cells converted to a primitive stem cell state within 7 to 14 days. Their techniques also were successful in experiments with blood cells from adult bone marrow and from circulating blood.

How useful is all of this?  If this procedure is indeed an efficient method to produce virus-free iPS cells the researchers believe that it will speed research to develop stem cell therapies, using nearly all cell types, and may provide a more accurate picture of cell development and biology.