Department of Internal Medicine, I.R.C.C.S. San Matteo Foundation and the University of Pavia, Pavia, Italy
Larissa Lordier
UMR 1170, Institut National de la Santé et de la Recherche Médicale, Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy Cancer Campus, Equipe Labellisée Ligue Nationale Contre le Cancer, Villejuif, France
Paolo M Soprano
Department of Molecular Medicine, University of Pavia, Pavia, Italy
Aikaterini Ntai
Integrated Systems Engineering, Milano, Italy; Isenet Biobanking, Milano, Italy
Serena Barozzi
Department of Internal Medicine, I.R.C.C.S. San Matteo Foundation and the University of Pavia, Pavia, Italy
Alberto La Spada
Integrated Systems Engineering, Milano, Italy; Isenet Biobanking, Milano, Italy
Ida Biunno
Isenet Biobanking, Milano, Italy; Institute for Genetic and Biomedical Research-CNR, Milano, Italy
Hana Raslova
UMR 1170, Institut National de la Santé et de la Recherche Médicale, Univ. Paris-Sud, Université Paris-Saclay, Gustave Roussy Cancer Campus, Equipe Labellisée Ligue Nationale Contre le Cancer, Villejuif, France
James B Bussel
Department of Pediatrics, Weill Cornell Medicine, New York, United States
Thrombocytopenic disorders have been treated with the Thrombopoietin-receptor agonist Eltrombopag. Patients with the same apparent form of thrombocytopenia may respond differently to the treatment. We describe a miniaturized bone marrow tissue model that provides a screening bioreactor for personalized, pre-treatment response prediction to Eltrombopag for individual patients. Using silk fibroin, a 3D bone marrow niche was developed that reproduces platelet biogenesis. Hematopoietic progenitors were isolated from a small amount of peripheral blood of patients with mutations in ANKRD26 and MYH9 genes, who had previously received Eltrombopag. The ex vivo response was strongly correlated with the in vivo platelet response. Induced Pluripotent Stem Cells (iPSCs) from one patient with mutated MYH9 differentiated into functional megakaryocytes that responded to Eltrombopag. Combining patient-derived cells and iPSCs with the 3D bone marrow model technology allows having a reproducible system for studying drug mechanisms and for individualized, pre-treatment selection of effective therapy in Inherited Thrombocytopenias.