Dynamic human erythropoiesis in a three-dimensional perfusion bone marrow biomimicry. (January 2019)

• Record Type: Journal Article
• Authors: Allenby, Mark C.; Panoskaltsis, Nicki; Tahlawi, Asma; Dos Santos, Susana Brito; Mantalaris, Athanasios
• Is Part Of: Biomaterials. Volume 188(2018)
• Page Start: 24
• Page End: 37
• Publication Date: 2019-01
• Subjects: Bone marrow -- Human hematopoiesis -- Erythropoiesis -- Cell therapy -- Image analysis -- Bioreactor; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2018.08.020
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Traditional culture systems for human erythropoiesis lack microenvironmental niches, spatial marrow gradients and dense cellularity rendering them incapable of effectively translating marrow physiology ex vivo . Herein, a bio-inspired three-dimensional (3D) perfusion bioreactor was engineered and inoculated with unselected single donor umbilical cord blood mononuclear cells (CBMNCs). Functional stromal and hematopoietic environments supporting long-term erythropoiesis were generated using defined medium supplemented only with stem cell factor (SCF) and erythropoietin (EPO) at near physiological concentrations. Quantitative 3D image analyses spatiotemporally mapped 21 multi-lineal cell distributions and interactions within multiple microenvironments that secreted extracellular matrix proteins and at least 16 endogenous hematopoietic and stromal growth factors. Tissue-like culture densities (≥2∙10 9 cells/mL), 1000-fold above flask cultures, were attained with continuous erythropoiesis and erythrocyte harvest. We propose this physiologically-relevant system for understanding normal and abnormal erythropoiesis, as well as for drug testing and/or discovery aimed at clinical translation.