Abstract:
: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.
journal_name
Bloodjournal_title
Bloodauthors
Di Buduo CA,Wray LS,Tozzi L,Malara A,Chen Y,Ghezzi CE,Smoot D,Sfara C,Antonelli A,Spedden E,Bruni G,Staii C,De Marco L,Magnani M,Kaplan DL,Balduini Adoi
10.1182/blood-2014-08-595561subject
Has Abstractpub_date
2015-04-02 00:00:00pages
2254-64issue
14eissn
0006-4971issn
1528-0020pii
blood-2014-08-595561journal_volume
125pub_type
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