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Stem Cells Transl Med. 2015 May;4(5):503-12. doi: 10.5966/sctm.2014-0244. Epub 2015 Apr 1.

Delayed minimally invasive injection of allogenic bone marrow stromal cell sheets regenerates large bone defects in an ovine preclinical animal model.

Author information

1
Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany.
2
Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany dietmar.hutmacher@qut.edu.au.

Abstract

Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future.

KEYWORDS:

Allogenic; Bone regeneration; Bone tissue engineering; Cell injection; Large bone defect; Mesenchymal stem cells; Sheep

PMID:
25834121
PMCID:
PMC4414222
DOI:
10.5966/sctm.2014-0244
[Indexed for MEDLINE]
Free PMC Article

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