title: An engineered multicomponent bone marrow niche for the recapitulation of hematopoiesis at ectopic transplantation sites.
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.
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.|Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Mónica S
authors.initials: MS
authors.lastname: Ventura Ferreira
authors.affiliation: Department of Dental Materials and Biomaterials Research, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bergmann
authors.affiliation: Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bodensiek
authors.affiliation: Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Peukert
authors.affiliation: Department of Dental Materials and Biomaterials Research, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Abert
authors.affiliation: Department of Clinical Immunology and Nephrology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.|Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Kramann
authors.affiliation: Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Kachel
authors.affiliation: Department of Orthopaedic Surgery, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Rath
authors.affiliation: Electron Microscopy Facility, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Rütten
authors.affiliation: Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Knuchel
authors.affiliation: Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.|Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Ebert
authors.affiliation: Department of Dental Materials and Biomaterials Research, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Fischer
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen, Germany. reschneider@ukaachen.de.|Institute of Pathology, University Hospital Aachen, RWTH Aachen University, Aachen, Germany. reschneider@ukaachen.de.|Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. reschneider@ukaachen.de.
authors.forename: Rebekka K
authors.initials: RK
authors.lastname: Schneider
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology*; D002130:Calcium Phosphates / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007797:Laminin; D059630:Mesenchymal Stem Cells / Q000502:physiology; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D010012:Osteogenesis / Q000502:physiology; D011509:Proteoglycans; D015203:Reproducibility of Results; D055153:Stem Cell Niche / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D002130:Calcium Phosphates; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C485817:beta-tricalcium phosphate; C059485:matrigel; D003094:Collagen
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