title: Human developmental chondrogenesis as a basis for engineering chondrocytes from pluripotent stem cells.
abstract: Joint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser-capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD166(low/neg)CD146(low/neg)CD73(+)CD44(low)BMPR1B(+)) distinguishing the earliest cartilage committed cells (prechondrocytes) at 5-6 weeks of development. Functional studies confirmed these cells are chondrocyte progenitors. From 12 weeks, only the superficial layers of articular cartilage were enriched in cells with this progenitor phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166(low/neg)BMPR1B(+) putative cartilage-committed progenitors. Taken as a whole, these data define a developmental approach for the generation of highly purified functional human chondrocytes from PSCs that could enable substantial progress in cartilage tissue engineering.
authors.affiliation: Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Laboratorio de Biología del Desarrollo Celular, Laboratorios de Investigación Aplicada en Nuerociencias, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Escobar B1625XAF, Buenos Aires, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Bluguermann
authors.affiliation: Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Levon
authors.initials: L
authors.lastname: Kyupelyan
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Brooke
authors.initials: B
authors.lastname: Latour
authors.affiliation: Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gonzalez
authors.affiliation: Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Saumya
authors.initials: S
authors.lastname: Shah
authors.affiliation: Broad Stem Cell Research Center, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Galic
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Sundi
authors.initials: S
authors.lastname: Ge
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Petrigliano
authors.affiliation: Broad Stem Cell Research Center, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Department of Medicine and Physiology, Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Nsair
authors.affiliation: Laboratorio de Biología del Desarrollo Celular, Laboratorios de Investigación Aplicada en Nuerociencias, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Escobar B1625XAF, Buenos Aires, Argentina.
authors.forename: Santiago G
authors.initials: SG
authors.lastname: Miriuka
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Lyons
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Broad Stem Cell Research Center, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Gay M
authors.initials: GM
authors.lastname: Crooks
authors.affiliation: Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: McAllister
authors.affiliation: Novogenix Laboratories, LLC, Los Angeles, CA 90033, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Van Handel
authors.affiliation: Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Broad Stem Cell Research Center, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Adams
authors.affiliation: Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Broad Stem Cell Research Center, University of California at Los Angeles, Los Angeles, CA 90095, USA ; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Evseenko
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D061346:Laser Capture Microdissection; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D023822:Tissue Engineering
chemical_list: D015415:Biomarkers