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J Hematol Oncol. 2016 Jan 25;9:4. doi: 10.1186/s13045-016-0234-9.

An engineered multicomponent bone marrow niche for the recapitulation of hematopoiesis at ectopic transplantation sites.

Author information

1
Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
2
Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
3
Department of Dental Materials and Biomaterials Research, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
4
Department of Clinical Immunology and Nephrology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
5
Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
6
Department of Orthopaedic Surgery, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
7
Electron Microscopy Facility, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
8
Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
9
Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA, USA.
10
Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen, Germany. reschneider@ukaachen.de.
11
Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany. reschneider@ukaachen.de.
12
Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. reschneider@ukaachen.de.

Abstract

BACKGROUND:

Bone marrow (BM) niches are often inaccessible for controlled experimentation due to their difficult accessibility, biological complexity, and three-dimensional (3D) geometry.

METHODS:

Here, we report the development and characterization of a BM model comprising of cellular and structural components with increased potential for hematopoietic recapitulation at ectopic transplantation sites. Cellular components included mesenchymal stromal cells (MSCs) and hematopoietic stem and progenitor cells (HSPCs). Structural components included 3D β-tricalcium phosphate (β-TCP) scaffolds complemented with Matrigel or collagen I/III gels for the recreation of the osteogenic/extracellular character of native BM.

RESULTS:

In vitro, β-TCP/Matrigel combinations robustly maintained proliferation, osteogenic differentiation, and matrix remodeling capacities of MSCs and maintenance of HSPCs function over time. In vivo, scaffolds promoted strong and robust recruitment of hematopoietic cells to sites of ectopic transplantation, vascularization, and soft tissue formation.

CONCLUSIONS:

Our tissue-engineered BM system is a powerful tool to explore the regulatory mechanisms of hematopoietic stem and progenitor cells for a better understanding of hematopoiesis in health and disease.

PMID:
26810307
PMCID:
PMC4727380
DOI:
10.1186/s13045-016-0234-9
[Indexed for MEDLINE]
Free PMC Article

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