The promise of Bone Marrow Erythroblast Cells for treating haematological diseases

The promise of Bone Marrow Erythroblast Cells for treating haematological diseases

Scheme of red blood cell formation: Nichols, Brendan & Shrestha, Rajiv & Horowitz, Joseph & Hollot, C.V. & Germain, Michael & Gaweda, Adam & Chait, Y. (2011). Simplification of an Erythropoiesis Model for Design of Anemia Management Protocols in End Stage Renal Disease. Conference proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. 2011. 83-6.

The treatment of severe anaemia and shock involves blood transfusion. Despite the availability of transfusable blood in developed countries, there are issues in terms of allogenic immune reactions that call for looking for less immunogenic options. Another challenge is the shortage of blood units in developing countries prompting alternatives such as deriving blood cells from autologous hematopoietic stem/progenitor cells. The sources of RBCs can be peripheral blood CD34+ cells or hematopoietic stem/progenitor cells. The major aspect of deriving the cells is enucleation. When synthesizing RBCs in the lab, a major critical step is the enucleation of erythroblasts.

The process of forming red blood cells (RBCs) is called erythropoiesis resulting in the formation of 2 million RBCs every second in healthy human adults. The bone marrow is the source of progenitors that become erythroid-committed precursors to finally mature RBC.

The erythroblastic islands are the sites of terminal erythropoiesis where erythroid-committed precursors undergo maturation. Several changes are seen in this process with the last stages being expulsion of the nuclei (enucleation) and organelles (mitochondria, endoplasmic reticulum, Golgi apparatus and ribosomes). This process of enucleation allows for efficient oxygen transport due to the lack of the nucleus. As these enucleated cells lack DNA, they do not undergo division to hence avoid the risk of malignancy in the recipients of blood transfusions.

2013-published research in Blood reported the technique to isolate erythroids at different stages of development. Primary bone marrow cultures could be used to isolate these cells using the markers GPA, band 3, and α4 integrin. Such cells in different stages could be isolated with high purity and large numbers. Detailed studies using sequencing on these cells can allow a detailed understanding of erythropoiesis and also for screening molecules that can target specific erythroid stages to treat diseases with altered erythropoiesis.

The use of human erythroid cultures can thus allow studying conditions with altered erythropoiesis like malaria, thalassemia and myelodysplastic syndrome. Such a detailed understanding of the mechanisms in erythropoiesis lays the foundation for treating haematological diseases.

References:

Moras M, Lefevre SD and Ostuni MA (2017) From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals. Front. Physiol. 8:1076. doi: 10.3389/fphys.2017.01076

Ganesan Keerthivasan, Amittha Wickrema, and John D. Crispino. Erythroblast Enucleation. Stem Cells International 2011. Article ID 139851: 9 pages.

Hu, J., Liu, J., Xue, F., Halverson, G., Reid, M., Guo, A., Chen, L., Raza, A., Galili, N., Jaffray, J., Lane, J., Chasis, J. A., Taylor, N., Mohandas, N., & An, X. (2013). Isolation and functional characterization of human erythroblasts at distinct stages: implications for understanding of normal and disordered erythropoiesis in vivo. Blood, 121(16), 3246–3253. https://doi.org/10.1182/blood-2013-01-476390

 

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