Possible treatment for sickle cell anemia with gene therapy and induced pluripotent stem cells

University of Michigan

Researchers are on the path to using both gene therapy and induced pluriopotent stem cell technology (iPSC) together to create a possible treatment for sickle cell anemia.  Sickle cell is a recessive genetic disorder that is cause by a single base mutation in the gene for hemoglobin.  This single base mutation changes the shape of the hemoglobin molecule which causes red blood cells to collapse into a sickle shape.  These sickle shaped red blood cells clog blood vessels causing pain, infections, organ damage and death.

Using a patient's own stem cells, researchers at Johns Hopkins have corrected the genetic alteration that causes sickle cell disease (SCD), a painful, disabling inherited blood disorder that affects mostly African-Americans. The corrected stem cells were coaxed into immature red blood cells in a test tube that then turned on a normal version of the gene....

Using one adult patient at The Johns Hopkins Hospital as their first case, the researchers first isolated the patient's bone marrow cells. After generating induced pluripotent stem (iPS) cells - adult cells that have been reprogrammed to behave like embryonic stem cells - from the bone marrow cells, they put one normal copy of the hemoglobin gene in place of the defective one using genetic engineering techniques. The beauty of iPS cells is that we can grow a lot of them and then coax them into becoming cells of any kind, including red blood cells," Cheng said.

In their process, his team converted the corrected iPS cells into immature red blood cells by giving them growth factors. Further testing showed that the normal hemoglobin gene was turned on properly in these cells, although at less than half of normal levels. "We think these immature red blood cells still behave like embryonic cells and as a result are unable to turn on high enough levels of the adult hemoglobin gene," explains Cheng. "We next have to learn how to properly convert these cells into mature red blood cells."