Open AccessNonintegrating Knockdown and Customized Scaffold Design Enhances Human Adipose‐Derived Stem Cells in Skeletal Repair
Author(s) -
Levi Benjamin,
Hyun Jeong S.,
Nelson Emily R.,
Li Shuli,
Montoro Daniel T.,
Wan Derrick C.,
Jia Fang Jun,
Glotzbach Jason C.,
James Aaron W.,
Lee Min,
Huang Mei,
Quarto Natalina,
Gurtner Geoffrey C.,
Wu Joseph C.,
Longaker Michael T.
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.757
Subject(s) - noggin , microbiology and biotechnology , biology , stem cell , regenerative medicine , gene knockdown , scaffold , small hairpin rna , homing (biology) , bone morphogenetic protein , bone morphogenetic protein 2 , adipose tissue , biomedical engineering , in vitro , cell culture , endocrinology , medicine , biochemistry , genetics , ecology , gene
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. S TEM C ells 2011;29:2018–2029.