title: Engineering bone tissue substitutes from human induced pluripotent stem cells.
abstract: Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSC-derived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease.
authors: The New York Stem Cell Foundation, New York, NY 10032, USA.
authors: Giuseppe Maria
authors: GM
authors: de Peppo
authors: Iván
authors: I
authors: Marcos-Campos
authors: David John
authors: DJ
authors: Kahler
authors: Dana
authors: D
authors: Alsalman
authors: Linshan
authors: L
authors: Shang
authors: Gordana
authors: G
authors: Vunjak-Novakovic
authors: Darja
authors: D
authors: Marolt
mesh_terms: D000818:Animals; D019149:Bioreactors; D001861:Bone Regeneration; D018786:Bone Substitutes; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009928:Organ Specificity; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D018786:Bone Substitutes
keywords: bone regeneration; dynamic culture; embryonic stem cells; mesodermal progenitors; microarray analysis
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