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

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.