Novel and Highly Efficient Production of Red Blood Cells
A new method to boost the efficiency of ex vivo production of red blood cells by silencing the gene SH2B3
Background
Transfusion of red blood cells (RBCs) is an extremely common medical procedure used for a variety of lifesaving applications. However, the supply of RBCs is completely dependent upon the frequency and quality of blood donations and blood banks are often in short supply. The ability to produce RBCs ex vivo from hematopoietic stem and progenitor cells (HSPCs) or pluripotent stem cells is a major area of research focused that could provide a more reliable alternative to our volatile blood supply.
Technology Overview
Researchers at Boston Children’s Hospital have developed a new method to boost the efficiency of ex vivo production of RBCs. By silencing the gene SH2B3, the researchers were able to boost RBC production from adult HSPCs and cord blood HSPCs by 2- to 7- fold. In addition, deleting SH2B3 in human pluripotent stem cells increased the yield of erythroid cells by 3-fold.
To achieve this result, the researchers used large-scale population genetics to identify that rare loss-of-function versions of the SH2B3 gene are linked to increased RBC counts in humans. The lab used two independent gene silencing techniques, shRNA and CRISPR/Cas9 genome editing, and found that knockdown of SH2B3 led to increased differentiation of HSPCs into mature RBCs ex vivo. These findings demonstrate that stable knockdown of SH2B3 can provide an improved method for generating RBCs.
Further Details:
Giani FC, Fiorini C, Wakabayashi A, et al. Targeted application of human genetic variation can improve red blood cell production from stem cells. Cell Stem Cell. 2016 Jan 7;18(1):73-78.
Benefits
Inhibition or disruption of SH2B3 function improves upon current ex vivo methods for RBC production by:
- Increasing the quality and quantity of RBCs
- Decreasing the number of HSPCs initially required to produce RBCs by an estimated one-fifth
- Decreasing the cost of RBC production
Applications
- Ex vivo method to produce RBCs from a population of stem or progenitor cells for use in blood transfusions or for the treatment of various disorders characterized by a deficiency of RBCs
- Research approach that uses population genetics to identify rare gene variants linked to altered levels of specific cell types to develop new ways to boost production of specific cells for use in regenerative medicine
Patents
IP Status
- Patent application submitted
