Engineering a human bone marrow model: a case study on ex vivo erythropoiesis.
Bone marrow, with its intricate, three-dimensional tissue structure facilitating cell-cell interactions, provides a microenvironment supporting the production of hundreds of billions of multilineal blood cells everyday. We have developed a three-dimensional bone marrow culture system in which marrow cells are cultured in a reactor packed with porous microspheres. The culture supports a three-dimensional growth configuration and multilineal hemopoiesis mimicking the bone marrow in vivo. We studied ex vivo human erythropoiesis using the three-dimensional culture system. The system sustained extensive erythropoiesis at low erythropoietin concentrations (0.2 U/mL), plus stem cell factor, interleukin-3, granulocyte-macrophage colony-stimulating factor, and insulin-like growth factor-I. Erythroid cell production lasted for more than 5 weeks, and the percentage of erythroid cells in the nonadherent cell population was approximately 60%. Flow cytometric analysis using cell surface markers specific for erythroid cells (CD71 and glycophorin-A) indicated that the culture produced early, intermediate, and late erythroid cells. As the culture progressed, the erythroid cell population shifted gradually toward mature cell types. When compared to the three-dimensional culture, the traditional flask cultures failed to support extensive erythropoiesis under the same conditions. This indicates that the three-dimensional bone marrow culture system provides a microenvironment conducive to erythropoiesis under more physiological conditions and is a better bone marrow model.
Mantalaris
A
A
Department of Chemical Engineering, University of Rochester, New York 14627-0166, USA.
Keng
P
P
Bourne
P
P
Chang
A Y
AY
Wu
J H
JH
D001698:Biomedical Engineering; D019149:Bioreactors; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008863:Microspheres; D008954:Models, Biological
D006133:Growth Substances