Journal
BLOOD
Volume 125, Issue 14, Pages 2254-2264Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2014-08-595561
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Funding
- Cariplo Foundation [2010-0807]
- National Institutes of Health, National Institute of Biomedical Imaging and Bioengeneering [EB016041-01]
- Italian Ministry of Health [RF-2009-1550218, RF-2010-2316198]
- Italian Ministry of University and Research
- Fondo per gli Investimenti della Ricerca di Base [RBFR1299KO]
- Associazione Italiana per la Ricerca sul Cancro (AIRC, Milano)
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We present a programmable bioengineered 3-dimensional silk-based bone marrow niche tissue system that successfully mimics the physiology of human bone marrow environment allowing us to manufacture functional human platelets ex vivo. Using stem/progenitor cells, megakaryocyte function and platelet generation were recorded in response to variations in extracellular matrix components, surface topography, stiffness, coculture with endothelial cells, and shear forces. Millions of human platelets were produced and showed to be functional based on multiple activation tests. Using adult hematopoietic progenitor cells our system demonstrated the ability to reproduce key steps of thrombopoiesis, including alterations observed in diseased states. A critical feature of the system is the use of natural silk protein biomaterial allowing us to leverage its biocompatibility, nonthrombogenic features, programmable mechanical properties, and surface binding of cytokines, extracellular matrix components, and endothelial-derived proteins. This in turn offers new opportunities for the study of blood component production ex vivo and provides a superior tissue system for the study of pathologic mechanisms of human platelet production.
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