Nonintegrating Knockdown and Customized Scaffold Design Enhances Human Adipose-Derived Stem Cells in Skeletal Repair

被引：62

作者：

Levi, Benjamin ^{[1
]}

Hyun, Jeong S. ^{[1
]}

Nelson, Emily R. ^{[1
]}

Li, Shuli ^{[1
]}

Montoro, Daniel T. ^{[1
]}

Wan, Derrick C. ^{[1
]}

Jia, Fang Jun ^{[2
]}

Glotzbach, Jason C. ^{[1
]}

James, Aaron W. ^{[1
]}

Lee, Min ^{[3
]}

Huang, Mei ^{[2
]}

Quarto, Natalina ^{[1
,4
]}

Gurtner, Geoffrey C. ^{[1
,5
]}

Wu, Joseph C. ^{[2
,5
]}

Longaker, Michael T. ^{[1
,5
]}

机构：

[1] Stanford Univ, Hagey Lab Pediat Regenerat Med, Sch Med, Div Plast & Reconstruct Surg,Dept Surg, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Med & Radiol, Sch Med, Stanford, CA 94305 USA

[3] Univ Calif Los Angeles, Sch Dent, Div Adv Prosthodont Biomat & Hosp Dent, Los Angeles, CA 90024 USA

[4] Univ Naples Federico II, Dipartimento Sci Chirurg Anestesiol Rianimatorie, Naples, Italy

[5] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

来源：

STEM CELLS | 2011年 / 29卷 / 12期

基金：

美国国家卫生研究院;

关键词：

Skeletal tissue engineering; Tissue regeneration; Multipotent stromal cells; Calvarial defect; Noggin; Bone morphogenetic protein; Scaffold; BONE MORPHOGENETIC PROTEIN-2; TISSUE-ENGINEERED BONE; GENE-THERAPY; IN-VITRO; MINICIRCLE VECTOR; DELIVERY; DIFFERENTIATION; DEFECTS; RHBMP-2; NOGGIN;

D O I：

10.1002/stem.757

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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

引用

页码：2018 / 2029

页数：12

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