title: Nonintegrating knockdown and customized scaffold design enhances human adipose-derived stem cells in skeletal repair.
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.
authors: Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, California 94305-5148, USA.
authors: Benjamin
authors: B
authors: Levi
authors: Jeong S
authors: JS
authors: Hyun
authors: Emily R
authors: ER
authors: Nelson
authors: Shuli
authors: S
authors: Li
authors: Daniel T
authors: DT
authors: Montoro
authors: Derrick C
authors: DC
authors: Wan
authors: Fang Jun
authors: FJ
authors: Jia
authors: Jason C
authors: JC
authors: Glotzbach
authors: Aaron W
authors: AW
authors: James
authors: Min
authors: M
authors: Lee
authors: Mei
authors: M
authors: Huang
authors: Natalina
authors: N
authors: Quarto
authors: Geoffrey C
authors: GC
authors: Gurtner
authors: Joseph C
authors: JC
authors: Wu
authors: Michael T
authors: MT
authors: Longaker
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000328:Adult; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D001861:Bone Regeneration; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020007:Implants, Experimental; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010012:Osteogenesis; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012886:Skull / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D055815:Young Adult; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D002352:Carrier Proteins; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D000099176:Noggin Protein; C525718:BMP2 protein, human