Journal
STEM CELLS
Volume 29, Issue 12, Pages 2018-2029Publisher
WILEY
DOI: 10.1002/stem.757
Keywords
Skeletal tissue engineering; Tissue regeneration; Multipotent stromal cells; Calvarial defect; Noggin; Bone morphogenetic protein; Scaffold
Categories
Funding
- National Institutes of Health, National Institute of Dental and Craniofacial Research [1 R21 DE019274-01, RC2 DE020771-01]
- Oak Foundation
- Hagey Laboratory for Pediatric Regenerative Medicine
- National Institutes of Health, National Institute of Arthritis, and Musculoskeletal and Skin Diseases [1F32AR057302-02]
- [R01EB009689]
- [RC1HL099117]
- [R33HL089027]
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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
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