title: Directed differentiation of human induced pluripotent stem cells toward bone and cartilage: in vitro versus in vivo assays.
abstract: The ability to differentiate induced pluripotent stem cells (iPSCs) into committed skeletal progenitors could allow for an unlimited autologous supply of such cells for therapeutic uses; therefore, we attempted to create novel bone-forming cells from human iPSCs using lines from two distinct tissue sources and methods of differentiation that we previously devised for osteogenic differentiation of human embryonic stem cells, and as suggested by other publications. The resulting cells were assayed using in vitro methods, and the results were compared with those obtained from in vivo transplantation assays. Our results show that true bone was formed in vivo by derivatives of several iPSC lines, but that the successful cell lines and differentiation methodologies were not predicted by the results of the in vitro assays. In addition, bone was formed equally well from iPSCs originating from skin or bone marrow stromal cells (also known as bone marrow-derived mesenchymal stem cells), suggesting that the iPSCs did not retain a "memory" of their previous life. Furthermore, one of the iPSC-derived cell lines formed verifiable cartilage in vivo, which likewise was not predicted by in vitro assays.
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Phillips
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Kuznetsov
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Cherman
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Kyeyoon
authors.initials: K
authors.lastname: Park
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Chen
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Britney N
authors.initials: BN
authors.lastname: McClendon
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Hamilton
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Ronald D G
authors.initials: RD
authors.lastname: McKay
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Josh G
authors.initials: JG
authors.lastname: Chenoweth
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Mallon
authors.affiliation: Craniofacial and Skeletal Diseases Branch, Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; The NIH Stem Cell Unit, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland, USA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, Maryland, USA probey@dir.nidcr.nih.gov.
authors.forename: Pamela G
authors.initials: PG
authors.lastname: Robey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001681:Biological Assay / Q000379:methods*; D002454:Cell Differentiation; D002460:Cell Line; D065150:Cellular Reprogramming; D019902:Chondrocytes / Q000378:metabolism* / Q000637:transplantation; D020219:Chondrogenesis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000637:transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism* / Q000637:transplantation; D010012:Osteogenesis; D010641:Phenotype; D014162:Transfection
keywords: Bone; Chondrogenesis; Induced pluripotent stem cells; Osteoblast; Transplantation