Runx2 overexpression in bone marrow stromal cells accelerates bone formation in critical-sized femoral defects.
The repair of large nonunions in long bones remains a significant clinical problem due to high failure rates and limited tissue availability for auto- and allografts. Many cell-based strategies for healing bone defects deliver bone marrow stromal cells (BMSCs) to the defect site to take advantage of the inherent osteogenic capacity of this cell type. However, many factors, including donor age and ex vivo expansion of the cells, cause BMSCs to lose their differentiation ability. To overcome these limitations, we have genetically engineered BMSCs to constitutively overexpress the osteoblast-specific transcription factor Runx2. In the present study, we examined Runx2-modified BMSCs, delivered via polycaprolactone scaffolds loaded with type I collagen meshes, in critical-sized segmental defects in rats compared to unmodified cells, cell-free scaffolds, and empty defects. Runx2 expression in BMSCs accelerated healing of critical-sized defects compared to unmodified BMSCs and defects receiving cell-free treatments. These findings provide an accelerated method for healing large bone defects, which may reduce recovery time and the need for external fixation of critical-sized defects.
Wojtowicz
Abigail M
AM
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Templeman
Kellie L
KL
Hutmacher
Dietmar W
DW
Guldberg
Robert E
RE
García
Andrés J
AJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000473:pathology* / Q000601:surgery; D005434:Flow Cytometry; D005818:Genetic Engineering / Q000379:methods*; D008297:Male; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D011091:Polyesters / Q000737:chemistry; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D017154:Stromal Cells / Q000166:cytology*; D054457:Tissue Scaffolds / Q000737:chemistry; D055114:X-Ray Microtomography
D050659:Core Binding Factor Alpha 1 Subunit; D011091:Polyesters; C493717:Runx2 protein, rat; C016240:polycaprolactone
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