Tissue engineered humanized bone supports human hematopoiesis in vivo

Holzapfel, Boris M., Hutmacher, Dietmar W., Nowlan, Bianca, Barbier, Valerie, Thibaudeau, Laure, Theodoropoulos, Christina, Hooper, John D., Loessner, Daniela, Clements, Judith A., Russell, Pamela J., Pettit, Allison R., Winkler, Ingrid G. and Levesque, Jean-Pierre (2015) Tissue engineered humanized bone supports human hematopoiesis in vivo. Biomaterials, 61 103-114. doi:10.1016/j.biomaterials.2015.04.057

Author Holzapfel, Boris M.
Hutmacher, Dietmar W.
Nowlan, Bianca
Barbier, Valerie
Thibaudeau, Laure
Theodoropoulos, Christina
Hooper, John D.
Loessner, Daniela
Clements, Judith A.
Russell, Pamela J.
Pettit, Allison R.
Winkler, Ingrid G.
Levesque, Jean-Pierre
Title Tissue engineered humanized bone supports human hematopoiesis in vivo
Formatted title
Tissue engineered humanized bone supports human hematopoiesis in vivo
Journal name Biomaterials   Check publisher's open access policy
ISSN 0142-9612
Publication date 2015-08
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.biomaterials.2015.04.057
Volume 61
Start page 103
End page 114
Total pages 12
Place of publication Elsevier
Publisher Amsterdam, Netherlands
Collection year 2016
Language eng
Abstract Advances in tissue-engineering have resulted in a versatile tool-box to specifically design a tailored microenvironment for hematopoietic stem cells (HSCs) in order to study diseases that develop within this setting. However, most current in vivo models fail to recapitulate the biological processes seen in humans. Here we describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the HSC niches. Ectopic implantation of biodegradable composite scaffolds cultured for 4 weeks with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone organ including a large number of human mesenchymal cells which were shown to be metabolically active and capable of establishing a humanized microenvironment supportive of the homing and maintenance of human HSCs. A syngeneic mouse-to-mouse transplantation assay was used to prove the functionality of the tissue-engineered ossicles. We predict that the ability to tissue engineer a morphologically intact and functional large-volume bone organ with a humanized bone marrow compartment will help to further elucidate physiological or pathological interactions between human HSCs and their native niches.
Keyword Tissue engineering
Humanized niche
Bone organ
Hematopoietic stem cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2016 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 20 Jul 2015, 15:09:52 EST by Joanne PRESTON on behalf of Mater Research Institute-UQ