Image by Ying Wang–
Johns Hopkins Medicine
Researchers say they have devised a technique for generating normal, mature red blood cells (RBCs) from patients with sickle cell disease (SCD).
The team hopes that, ultimately, the RBCs could be transfused back into the patients from which they are derived and eliminate the need for donor transfusion in SCD.
Linzhao Cheng, PhD, of the Johns Hopkins School of Medicine in Baltimore, Maryland, and his colleagues described the technique in Stem Cells.
Dr Cheng noted that SCD patients often require RBC transfusions, but over time, their bodies may begin to mount an immune response against the foreign blood.
“Their bodies quickly kill off the blood cells,” Dr Cheng said. “So they have to get transfusions more and more frequently.”
A solution, Dr Cheng and his colleagues thought, would be to generate RBCs for transfusion using a patient’s own cells.
To do this, the researchers first took hematopoietic cells from an SCD patient and generated induced pluripotent stem cells (iPSCs).
Then, the team used the gene-editing technique CRISPR/Cas9 to target the homozygous SCD mutation (nt. 69A>T) in the HBB gene and ensure the RBCs they generated would not be sickled.
Finally, they coaxed the iPSCs into mature RBCs that expressed the corrected HBB gene. The edited iPSCs generated RBCs just as efficiently as iPSCs that hadn’t been subjected to CRISPR/Cas9.
And the level of HBB protein expression in the RBCs derived from edited iPSCs was similar to that of RBCs generated from unedited iPSCs.
Dr Cheng noted that, to become medically useful, this method will have to be made more efficient and scaled up significantly. And the cells would need to be tested for safety.
“[Nevertheless,] this study shows it may be possible in the not-too-distant future to provide patients with sickle cell disease with an exciting new treatment option,” Dr Cheng said.
He and his colleagues believe this method of RBC generation may also be applicable for other blood disorders. And they think it might be possible to edit cells from healthy individuals so they can resist malaria and other infectious agents.
Another research group has reported the ability to correct the SCD mutation using zinc-finger nucleases.
