title: Single-stage cell-based cartilage regeneration using a combination of chondrons and mesenchymal stromal cells: comparison with microfracture.
abstract: BACKGROUND
  Autologous chondrocyte implantation (ACI) is traditionally a 2-step procedure used to repair focal articular cartilage lesions. With use of a combination of chondrons (chondrocytes in their own territorial matrix) and mesenchymal stromal cells (MSCs), ACI could be innovated and performed in a single step, as sufficient cells would be available to fill the defect within a 1-step surgical procedure. Chondrons have been shown to have higher regenerative capacities than chondrocytes without such a pericellular matrix.
  
  
  OBJECTIVE
  To evaluate cartilage formation by a combination of chondrons and MSCs in vitro and in both small and large animal models.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Chondrons and MSCs were cultured at different ratios in vitro containing 0%, 5%, 10%, 20%, 50%, or 100% chondrons (n = 3); embedded in injectable fibrin glue (Beriplast); and implanted subcutaneously in nude mice (n = 10; ratios of 0%, 5%, 10%, and 20% chondrons). Also, in a 1-step procedure, a combination of chondrons and MSCs was implanted in a freshly created focal articular cartilage lesion (10% chondrons) in goats (n = 8) and compared with microfracture. The effect of both treatments, after 6-month follow-up, was evaluated using biochemical glycosaminoglycan (GAG) and GAG/DNA analysis and scored using validated scoring systems for macroscopic and microscopic defect repairs.
  
  
  RESULTS
  The addition of MSCs to chondron cultures enhanced cartilage-specific matrix production as reflected by a higher GAG production (P < .03), both in absolute levels and normalized to DNA content, compared with chondrocyte and 100% chondron cultures. Similar results were observed after 4 weeks of subcutaneous implantation in nude mice. Treatment of freshly created cartilage defects in goats using a combination of chondrons and MSCs in Beriplast resulted in better microscopic, macroscopic, and biochemical cartilage regeneration (P ≤ .02) compared with microfracture treatment.
  
  
  CONCLUSIONS
  The combination of chondrons and MSCs increased cartilage matrix formation, and this combination of cells was safely applied in a goat model for focal cartilage lesions, outperforming microfracture.
  
  
  CONCLUSIONS
  This study describes the bench-to-preclinical development of a new cell-based regenerative treatment for focal articular cartilage defects that outperforms microfracture in goats. In addition, it is a single-step procedure, thereby making the expensive cell expansion and reimplantation of dedifferentiated cells, as in ACI, redundant.
authors.affiliation: Department of Orthopaedics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Joris E J
authors.initials: JE
authors.lastname: Bekkers
authors.forename: Anika I
authors.initials: AI
authors.lastname: Tsuchida
authors.forename: Mattie H P
authors.initials: MH
authors.lastname: van Rijen
authors.forename: Lucienne A
authors.initials: LA
authors.lastname: Vonk
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Laura B
authors.initials: LB
authors.lastname: Creemers
authors.forename: Daniel B F
authors.initials: DB
authors.lastname: Saris
mesh_terms: D000818:Animals; D054544:Arthroplasty, Subchondral; D002356:Cartilage / Q000502:physiology* / Q000637:transplantation; D002469:Cell Separation; D019902:Chondrocytes / Q000637:transplantation*; D018920:Coculture Techniques; D005260:Female; D006041:Goats; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D008819:Mice, Nude; D012038:Regeneration; D019737:Transplants
keywords: 1 step; ACI; MSC; chondron; regeneration