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Local transplantation is an effective method for cell delivery in the osteogenesis imperfecta murine model

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Abstract

Purpose

Osteogenesis imperfecta is a serious genetic disorder that results from improper type I collagen production. We aimed to evaluate whether bone marrow stromal cells (BMSC) delivered locally into femurs were able to engraft, differentiate into osteoblasts, and contribute to formation of normal bone matrix in the osteogenesis imperfect murine (oim) model.

Methods

Donor BMSCs from bone-specific reporter mice (Col2.3GFP) were expanded in vitro and transplanted into the femoral intramedullary cavity of oim mice. Engraftment was evaluated after four weeks.

Results

We detected differentiation of donor BMSCs into Col2.3GFP+ osteoblasts and osteocytes in cortical and trabecular bone of transplanted oim femurs. New bone formation was detected by deposition of dynamic label in the proximity to the Col2.3GFP+ osteoblasts, and new bone showed more organized collagen structure and expression of type I α2 collagen. Col2.3GFP cells were not found in the contralateral femur indicating that transplanted osteogenic cells did not disseminate by circulation. No osteogenic engraftment was observed following intravenous transplantation of BMSCs. BMSC cultures derived from transplanted femurs showed numerous Col2.3GFP+ colonies, indicating the presence of donor progenitor cells. Secondary transplantation of cells recovered from recipient femurs and expanded in vitro also showed Col2.3GFP+ osteoblasts and osteocytes confirming the persistence of donor stem/progenitor cells.

Conclusion

We show that BMSCs delivered locally in oim femurs are able to engraft, differentiate into osteoblasts and osteocytes and maintain their progenitor potential in vivo. This suggests that local delivery is a promising approach for introduction of autologous MSC in which mutations have been corrected.

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Acknowledgments

This work has been supported by NIH/NIAMS grant AR055607 to I.K and a Fellows Research Award by Connecticut Children’s Medical Center to P.P. We would like to thank Dr. Charlotte Phillips, University of Missouri–Columbia for providing the collagen type I α2 chain antibody.

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Authors and Affiliations

  1. Department of Reconstructive Sciences, MC 3705, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT, 06032, USA

    Penelope Pauley, Brya G. Matthews, Liping Wang, Nathaniel A. Dyment, Igor Matic, David W. Rowe & Ivo Kalajzic

  2. Connecticut Children’s Medical Center, Hartford, CT, USA

    Penelope Pauley

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  1. Penelope Pauley
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  2. Brya G. Matthews
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  3. Liping Wang
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  4. Nathaniel A. Dyment
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  5. Igor Matic
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  6. David W. Rowe
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  7. Ivo Kalajzic
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Correspondence to Ivo Kalajzic.

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Pauley, P., Matthews, B.G., Wang, L. et al. Local transplantation is an effective method for cell delivery in the osteogenesis imperfecta murine model. International Orthopaedics (SICOT) 38, 1955–1962 (2014). https://doi.org/10.1007/s00264-013-2249-y

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  • DOI: https://doi.org/10.1007/s00264-013-2249-y

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