title: Porcine intervertebral disc repair using allogeneic juvenile articular chondrocytes or mesenchymal stem cells.
abstract: Tissue engineering strategies for intervertebral disc repair have focused on the use of autologous disc-derived chondrocytes. Difficulties with graft procurement, harvest site morbidity, and functionality, however, may limit the utility of this cell source. We used an in vivo porcine model to investigate allogeneic non-disc-derived chondrocytes and allogeneic mesenchymal stem cells (MSCs) for disc repair. After denucleation, lumbar discs were injected with either fibrin carrier alone, allogeneic juvenile chondrocytes (JCs), or allogeneic MSCs. Discs were harvested at 3, 6, and 12 months, and cell viability and functionality were assessed qualitatively and quantitatively. JC-treated discs demonstrated abundant cartilage formation at 3 months, and to a lesser extent at 6 and 12 months. For the carrier and MSC-treated groups, however, there was little evidence of proteoglycan matrix or residual notochordal/chondrocyte cells, but rather a type I/II collagen-enriched scar tissue. By contrast, JCs produced a type II collagen-rich matrix that was largely absent of type I collagen. Viable JCs were observed at all time points, whereas no evidence of viable MSCs was found. These data support the premise that committed chondrocytes are more appropriate for use in disc repair, as they are uniquely suited for survival in the ischemic disc microenvironment.
authors.affiliation: Orthopaedic Bioengineering Laboratory, University of California, San Francisco, CA 94143, USA.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Acosta
authors.forename: Lionel
authors.initials: L
authors.lastname: Metz
authors.forename: Huston Davis
authors.initials: HD
authors.lastname: Adkisson
authors.forename: Jane
authors.initials: J
authors.lastname: Liu
authors.forename: Ellen
authors.initials: E
authors.lastname: Carruthers-Liebenberg
authors.forename: Curt
authors.initials: C
authors.lastname: Milliman
authors.forename: Michael
authors.initials: M
authors.lastname: Maloney
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Lotz
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D020219:Chondrogenesis; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007403:Intervertebral Disc / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D034421:Sus scrofa; D014184:Transplantation, Homologous; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D006025:Glycosaminoglycans; D008565:Membrane Proteins; C013786:A73025; D004247:DNA