title: Preferential therapy for osteoarthritis by cord blood MSCs through regulation of chondrogenic cytokines.
abstract: Osteoarthritis (OA) is a common rheumatic disease associated with imbalanced cartilage homeostasis which could be corrected by mesenchymal stem cells (MSCs) therapy. However, MSCs from different origins might exhibit distinct differentiation capacities. This study was undertaken to compare the therapeutic efficacies between MSCs from cord blood (CB-MSCs) and bone marrow (BM-MSCs) on OA treatment. The surface phenotypes and multipotent capacities of CB-MSCs and BM-MSCs were first characterized. The coculture commitment system was subsequently utilized for comparing the patterned molecules in stage-specific chondrogenesis of committed MSCs. For examining the therapeutic efficacies, committed CB-MSCs and BM-MSCs were encapsulated in neo-cartilage and subjected into pro-inflammatory cytokine environment. Finally, chondrogenic and inflammatory cytokine profiles in committed MSCs were evaluated. CB-MSCs and BM-MSCs were both negative for hematopoietic markers and positive for adhesion and mesenchymal cell markers. The CB-MSCs showed a markedly higher chondrogenic potential and relatively lower osteogenic and adipogenic capacities than BM-MSCs. During chondrogenesis, the committed CB-MSCs also showed significant increases in cell proliferation, adhesion molecules, signaling molecules, and chondrogenic-specific gene expressions in a coculture system. For the therapeutic efficacies, the committed CB-MSCs could strongly recover the pro-inflammatory cytokines diminished-Col II and proteoglycan expressions in a 3D arthritic model. The IL-10, ICAM-1 and TGF-β1 were also up-regulated in committed CB-MSCs analyzed by using cytokine profiling. Our data demonstrate that CB-MSCs possess specific advantages in cartilage regeneration over BM-MSCs. The CB-MSCs showed a better therapeutic potential that can contribute to advanced cell-based transplantation for clinical OA therapy.
authors.affiliation: Department of Neurosurgery, Taipei Medical University Hospital, Taipei, Taiwan, ROC.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Lo
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Chen
authors.forename: Tzu-Chieh
authors.initials: TC
authors.lastname: Lin
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.forename: Wei-Che
authors.initials: WC
authors.lastname: Hsu
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Chiang
authors.forename: Ming-Che
authors.initials: MC
authors.lastname: Liu
authors.forename: David F
authors.initials: DF
authors.lastname: Williams
authors.forename: Win-Ping
authors.initials: WP
authors.lastname: Deng
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology; D002356:Cartilage / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D019902:Chondrocytes / Q000473:pathology; D020219:Chondrogenesis; D016207:Cytokines / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008954:Models, Biological; D010003:Osteoarthritis / Q000628:therapy*
chemical_list: D016207:Cytokines