title: The effect of ex vivo dynamic loading on the osteogenic differentiation of genetically engineered mesenchymal stem cell model.
abstract: Mechanical loading has been described as a highly important stimulus for improvements in the quality and strength of bone. It has also been shown that mechanical stimuli can induce the differentiation of mesenchymal stem cells (MSCs) along the osteogenic lineage. We have previously demonstrated the potent osteogenic effect of MSCs engineered to overexpress the BMP2 gene. In this study we investigated the effect of mechanical loading on BMP2-expressing MSC-like cells, using a special bioreactor designed to apply dynamic forces on cell-seeded hydrogels. Cell viability, alkaline phosphatase (ALP) activity, BMP2 secretion and mineralized substance formation in the hydrogels were quantified. We found that cell metabolism increased as high as 6.8-fold, ALP activity by 12.5-fold, BMP2 secretion by 182-fold and mineralized tissue formation by 1.72-fold in hydrogels containing MSC-like cells expressing BMP2, which were cultured in the presence of mechanical loading. We have shown that ex vivo mechanical loading had an additive effect on BMP2-induced osteogenesis in genetically engineered MSC-like cells. These data could be valuable for bone tissue-engineering strategies of the future.
authors.affiliation: Skeletal Biotech Laboratory, Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem, Israel.
authors.forename: Nadav
authors.initials: N
authors.lastname: Kimelman-Bleich
authors.forename: Dror
authors.initials: D
authors.lastname: Seliktar
authors.forename: Ilan
authors.initials: I
authors.lastname: Kallai
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Helm
authors.forename: Zulma
authors.initials: Z
authors.lastname: Gazit
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
authors.forename: Gadi
authors.initials: G
authors.lastname: Pelled
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D019149:Bioreactors; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D005340:Fibrinogen / Q000737:chemistry; D005818:Genetic Engineering / Q000379:methods*; D020100:Hydrogels; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008809:Mice, Inbred C3H; D010012:Osteogenesis; D011092:Polyethylene Glycols / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D020100:Hydrogels; D011092:Polyethylene Glycols; D005340:Fibrinogen; D000469:Alkaline Phosphatase