Abstract
In this study, we examined the effectiveness of systemic subcutaneous delivery of recombinant Insulin-like growth factor (IGF)-I concurrently with primary cultured bone marrow-derived mesenchymal stem cell (MSC) transplant on fracture repair. We found that the fracture callus volume increased in mice with a stabilized tibia fracture that received IGF-I+MSC when compared with that in either untreated or MSC alone treated mice. In evaluating the callus tissue components, we found that the soft and new bone tissue volumes were significantly increased in IGF-I+MSC recipients. Histological and in-situ hybridization analyses confirmed a characteristic increase of newly forming bone in IGF-I+MSC recipients and that healing progressed mostly through endochondral ossification. The increase in soft and new bone tissue volumes correlated with increased force and toughness as determined by biomechanical testing. In conclusion, MSC transplant concurrent with systemic delivery of IGF-I improves fracture repair suggesting that IGF-I+MSC could be a novel therapeutic approach in patients who have inadequate fracture repair.
Acknowledgements
The authors would like to thank Dr G. Karsenty for providing probes for Col 1a1 and Osterix and Dr D.G. Mortlock for providing the probe for Col10.
Declaration of interest: This work was supported by NIH NIDDK R01 5R01DK070929-06 to A. Spagnoli and by the Pediatric Endocrine Society (Lawson Wilkins Pediatric Endocrine Society) Research Fellow Award 2010–2011 to Y. Yan. All authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.