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

Stem Cells. 2011 Dec;29(12):2018-29. doi: 10.1002/stem.757.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Adipose Tissue / metabolism
  • Adult
  • Animals
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Regeneration*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Differentiation
  • Female
  • Gene Knockdown Techniques
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Implants, Experimental
  • Lactic Acid / chemistry
  • Lactic Acid / metabolism
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • Male
  • Mice
  • Mice, Nude
  • Mice, Transgenic / genetics
  • Mice, Transgenic / metabolism
  • Middle Aged
  • Osteogenesis*
  • Polyglycolic Acid / chemistry
  • Polyglycolic Acid / metabolism
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Skull / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Time Factors
  • Tissue Engineering / methods
  • Tissue Scaffolds / chemistry*
  • Young Adult

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Carrier Proteins
  • RNA, Small Interfering
  • Recombinant Proteins
  • noggin protein
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid