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Intraoperative engineering of osteogenic grafts combining freshly harvested, human adipose-derived cells and physiological doses of bone morphogenetic protein-2

Mehrkens, A. and Saxer, F. and Guven, S. and Hoffmann, W. and Muller, A. M. and Jakob, M. and Weber, F. E. and Martin, I. and Scherberich, A.. (2012) Intraoperative engineering of osteogenic grafts combining freshly harvested, human adipose-derived cells and physiological doses of bone morphogenetic protein-2. European cells & materials, 24. pp. 308-319.

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Official URL: http://edoc.unibas.ch/dok/A6338296

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Abstract

Engineered osteogenic constructs for bone repair typically involve complex and costly processes for cell expansion. Adipose tissue includes mesenchymal precursors in large amounts, in principle allowing for an intraoperative production of osteogenic grafts and their immediate implantation. However, stromal vascular fraction (SVF) cells from adipose tissue were reported to require a molecular trigger to differentiate into functional osteoblasts. The present study tested whether physiological doses of recombinant human BMP-2 (rhBMP-2) could induce freshly harvested human SVF cells to generate ectopic bone tissue. Enzymatically dissociated SVF cells from 7 healthy donors (1 x 10(6) or 4 x 10(6)) were immediately embedded in a fibrin gel with or without 250 ng rhBMP-2, mixed with porous silicated calcium-phosphate granules (Actifuse((R)), Apatech) (final construct size: 0.1 cm(3)) and implanted ectopically for eight weeks in nude mice. In the presence of rhBMP-2, SVF cells not only supported but directly contributed to the formation of bone ossicles, which were not observed in control cell-free, rhBMP-2 loaded implants. In vitro analysis indicated that rhBMP-2 did not involve an increase in the percentage of SVF cells recruited to the osteogenic lineage, but rather induced a stimulation of the osteoblastic differentiation of the committed progenitors. These findings confirm the feasibility of generating fully osteogenic grafts using an easily accessible autologous cell source and low amounts of rhBMP-2, in a timing compatible with an intraoperative schedule. The study warrants further investigation at an orthotopic site of implantation, where the delivery of rhBMP-2 could be bypassed thanks to the properties of the local milieu.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Tissue Engineering (Martin)
UniBasel Contributors:Martin, Ivan
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:AO Research Institute Davos
e-ISSN:1473-2262
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:30 Nov 2017 10:40
Deposited On:10 Apr 2015 09:12

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