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Tissue-Specific Stem Cells
Article first published online: 16 NOV 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 12, pages 2018–2029, December 2011
How to Cite
Levi, B., Hyun, J. S., Nelson, E. R., Li, S., Montoro, D. T., Wan, D. C., Jia, F. J., Glotzbach, J. C., James, A. W., Lee, M., Huang, M., Quarto, N., Gurtner, G. C., Wu, J. C. and Longaker, M. T. (2011), Nonintegrating Knockdown and Customized Scaffold Design Enhances Human Adipose-Derived Stem Cells in Skeletal Repair. STEM CELLS, 29: 2018–2029. doi: 10.1002/stem.757
Author contributions: B.L. and D.C.W.: conception and design, administrative support, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; E.N.: administrative support, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; S.L., J.S.H., F.J., M.H., and J.P.G.: collection and/or assembly of data and data analysis and interpretation; A.W.J.: collection and/or assembly of data, data analysis and interpretation, and manuscript writing; D.T.M.: collection and/or assembly of data; M.L.: provision of study material or patients; N.Q.: conception and design, administrative support, collection and/or assembly of data, and data analysis and interpretation; G.C.G., J.C.W. and M.T.L.: conception and design and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS October 13, 2011.
- Issue published online: 16 NOV 2011
- Article first published online: 16 NOV 2011
- Accepted manuscript online: 13 OCT 2011 09:37AM EST
- Manuscript Accepted: 14 SEP 2011
- Manuscript Received: 27 JUN 2011
- National Institutes of Health
- National Institute of Dental and Craniofacial Research. Grant Numbers: 1 R21 DE019274-01, RC2 DE020771-01
- Oak Foundation and Hagey Laboratory for Pediatric Regenerative Medicine. Grant Numbers: R01EB009689, RC1HL099117, R33HL089027
- National Institute of Arthritis, and Musculoskeletal and Skin Diseases. Grant Number: 1F32AR057302-02
- Nog/Cre transgenic mice were a kind gift of Lisa Brunet and the Richard Harland Laboratory at the University of California at Berkeley
- Skeletal tissue engineering;
- Tissue regeneration;
- Multipotent stromal cells;
- Calvarial defect;
- Bone morphogenetic protein;
An urgent need exists in clinical medicine for suitable alternatives to available techniques for bone tissue repair. Human adipose-derived stem cells (hASCs) represent a readily available, autogenous cell source with well-documented in vivo osteogenic potential. In this article, we manipulated Noggin expression levels in hASCs using lentiviral and nonintegrating minicircle short hairpin ribonucleic acid (shRNA) methodologies in vitro and in vivo to enhance hASC osteogenesis. Human ASCs with Noggin knockdown showed significantly increased bone morphogenetic protein (BMP) signaling and osteogenic differentiation both in vitro and in vivo, and when placed onto a BMP-releasing scaffold embedded with lentiviral Noggin shRNA particles, hASCs more rapidly healed mouse calvarial defects. This study therefore suggests that genetic targeting of hASCs combined with custom scaffold design can optimize hASCs for skeletal regenerative medicine. STEM Cells 2011;29:2018–2029.