A three-dimensional in vitro model of erythropoiesis recapitulates erythroid failure in myelodysplastic syndromes.

Leukemia
Edda María ElvarsdóttirEva Hellström-Lindberg

Abstract

Established cell culture systems have failed to accurately recapitulate key features of terminal erythroid maturation, hampering our ability to in vitro model and treat diseases with impaired erythropoiesis such as myelodysplastic syndromes with ring sideroblasts (MDS-RS). We developed an efficient and robust three-dimensional (3D) scaffold culture model supporting terminal erythroid differentiation from both mononuclear (MNC) or CD34+-enriched primary bone marrow cells from healthy donors and MDS-RS patients. While CD34+ cells did not proliferate beyond two weeks in 2D suspension cultures, the 3D scaffolds supported CD34+ and MNC erythroid proliferation over four weeks demonstrating the importance of the 3D environment. CD34+ cells cultured in 3D facilitated the highest expansion and maturation of erythroid cells, including generation of erythroblastic islands and enucleated erythrocytes, while MNCs supported multi-lineage hemopoietic differentiation and cytokine secretion relevant for MDS-RS. Importantly, MDS-RS 3D-cultures supported de novo generation of ring sideroblasts and maintenance of the mutated clone. The 3D cultures effectively model a clonal disease characterized by terminal erythroid failure and can be used to ass...Continue Reading

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Citations

May 23, 2020·Haematologica·Eva Hellström-LindbergPeter Greenberg
Jul 30, 2020·International Journal of Molecular Sciences·Cécile DeleschauxMariano A Ostuni

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Methods Mentioned

BETA
MDS
xenograft
density gradient centrifugation
flow cytometry
confocal microscopy

Software Mentioned

GraphPad Prism
Panoramic Viewer
NIS Element

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