Programmable 3D silk bone marrow niche for platelet generation ex vivo and modeling of megakaryopoiesis pathologies.

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

Blood

journal_title

Blood

authors

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 A

doi

10.1182/blood-2014-08-595561

subject

Has Abstract

pub_date

2015-04-02 00:00:00

pages

2254-64

issue

14

eissn

0006-4971

issn

1528-0020

pii

blood-2014-08-595561

journal_volume

125

pub_type

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