Blood, 2015-04, Vol.125 (14), p.2254-2264
2015
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Details
- Autor(en) / Beteiligte
- Titel
- Programmable 3D silk bone marrow niche for platelet generation ex vivo and modeling of megakaryopoiesis pathologies
- Ist Teil von
- Blood, 2015-04, Vol.125 (14), p.2254-2264
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2015
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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. •Natural silk protein sponge and vascular tubes reproduce human bone marrow niche environments for functional platelet generation ex vivo.•Programmable bioengineered model for the investigation and therapeutic targeting of altered platelet formation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-4971eISSN: 1528-0020DOI: 10.1182/blood-2014-08-595561Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4383799
- Format
- –
- Schlagworte
- Adult, Animals, Blood Platelets - cytology, Blood Platelets - metabolism, Bombyx, Bone Marrow Cells - cytology, Bone Marrow Cells - metabolism, Cells, Cultured, Coculture Techniques, Endothelium, Vascular - cytology, Endothelium, Vascular - metabolism, Extracellular Matrix, Flow Cytometry, Hematopoietic Stem Cells - cytology, Hematopoietic Stem Cells - metabolism, Humans, Megakaryocytes - cytology, Megakaryocytes - metabolism, Platelets and Thrombopoiesis, Primary Myelofibrosis - metabolism, Primary Myelofibrosis - pathology, Silk - chemistry, Thrombopoiesis - physiology, Tissue Engineering, Tissue Scaffolds - chemistry