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Adipose-derived adult stromal cells heal critical-size mouse calvarial defects

Abstract

In adults and children over two years of age, large cranial defects do not reossify successfully, posing a substantial biomedical burden. The osteogenic potential of bone marrow stromal (BMS) cells has been documented. This study investigates the in vivo osteogenic capability of adipose-derived adult stromal (ADAS) cells, BMS cells, calvarial-derived osteoblasts and dura mater cells to heal critical-size mouse calvarial defects. Implanted, apatite-coated, PLGA scaffolds seeded with ADAS or BMS cells produced significant intramembranous bone formation by 2 weeks and areas of complete bony bridging by 12 weeks as shown by X-ray analysis, histology and live micromolecular imaging. The contribution of implanted cells to new bone formation was 84–99% by chromosomal detection. These data show that ADAS cells heal critical-size skeletal defects without genetic manipulation or the addition of exogenous growth factors.

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Figure 1: X-ray, alizarin red and histological analysis of specimens at 4 weeks.
Figure 2: Proliferation and bone formation of ADS and BMS cells.
Figure 3: Intramembranous versus endochondral bone formation.
Figure 4: Live micro-CT imaging.
Figure 5: Bone metabolic activity of animals implanted with control (no cells) or ADS cell–seeded scaffolds as determined by radiolabeled MDP incorporation overlaid with micro-CT images.

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Acknowledgements

This work has been supported by a grant from the National Institutes of Health (R01DE-14526) and the Oak foundation to M.T.L. The authors would like to thank Randall P. Nacamuli for his scientific and editorial assistance. We also acknowledge Koji Iwata and Michael Goris for their assistance with small animal imaging.

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Correspondence to Michael T Longaker.

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Cowan, C., Shi, YY., Aalami, O. et al. Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nat Biotechnol 22, 560–567 (2004). https://doi.org/10.1038/nbt958

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