Stromal cell derived factor-1α (SDF-1α) directed chemoattraction of transiently CXCR4 overexpressing mesenchymal stem cells into functionalized three-dimensional biomimetic scaffolds

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  • S Thieme, Department of Pediatrics, University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany
  • Martin Ryser, Department of Pediatrics, University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany
  • Marcus Gentsch, Department of Pediatrics, University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany
  • Katrin Navratiel, Department of Pediatrics, University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany
  • Sebastian Brenner, Department of Pediatrics, University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany
  • Jan Rölfing
  • Maik Stiehler, Dept. of Orthopaedics,University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany
  • Michael Gelinsky, DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD, Germany
  • Angela Rösen-Wolff, Department of Pediatrics, University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany
  • Ortopædkirurgisk Forskningslaboratorium
Three-dimensional (3D) bone substitute material should not only serve as scaffold in large bone defects but also attract mesenchymal stem cells, a subset of bone marrow stromal cells (BMSCs) that are able to form new bone tissue. An additional crucial step is to attract BMSCs from the surface into deeper structures of 3D porous bone substitute scaffolds. Here we show that transient overexpression of CXCR4 in human BMSCs induced by mRNA transfection enhances stromal cell-derived factor-1alpha (SDF-1alpha)-directed chemotactic capacity to invade internal compartments of porous 3D bone substitute scaffolds in vitro and in vivo. In vitro native BMCSs invaded up to 500 mum into SDF-1alpha-releasing 3D scaffolds, whereas CXCR4-overexpressing BMSCs invaded up to 800 mum within 5 days. In addition, 60% downregulation of endogenous SDF-1 transcription in BMSCs by endoribonuclease-prepared siRNA before CXCR4 mRNA transfection enhanced SDF-1alpha-directed migration of human BMSCs by 50%. Implantation of SDF-1alpha-releasing scaffolds seeded with transiently CXCR4-overexpressing BMSCs resulted in an increase of invasion into internal compartments of the scaffolds in a mouse model. In vivo native BMCS invaded up to 250 mum into SDF-1alpha-releasing 3D scaffolds, whereas CXCR4-overexpressing BMSC invaded up to 500 mum within 5 days. Thus, the SDF-1alpha/CXCR4 chemoattraction system can be used to efficiently recruit BMSCs into SDF-1alpha-releasing 3D scaffolds in vitro and in vivo.
Original languageEnglish
JournalTissue Engineering. Part C. Methods
Volume15
Issue4
Pages (from-to)687-96
Number of pages9
ISSN1937-3384
Publication statusPublished - 2009

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