Nonintegrating knockdown and customized scaffold design enhances human adipose-derived stem cells in skeletal repair

Benjamin Levi, Jeong S. Hyun, Emily R. Nelson, Shuli Li, Daniel T. Montoro, Derrick C. Wan, Fang Jun Jia, Jason C. Glotzbach, Aaron W. James, Min Lee, Mei Huang, Natalina Quarto, Geoffrey C. Gurtner, Joseph C. Wu, Michael T. Longaker

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2018-2029
Number of pages12
JournalSTEM CELLS
Volume29
Issue number12
DOIs
StatePublished - Dec 2011
Externally publishedYes

Keywords

  • Bone morphogenetic protein
  • Calvarial defect
  • Multipotent stromal cells
  • Noggin
  • Scaffold
  • Skeletal tissue engineering
  • Tissue regeneration

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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