title: Isolation and ex vivo expansion of synovial mesenchymal stromal cells for cartilage repair.
abstract: OBJECTIVE
  Hyaline articular cartilage is a highly specialized tissue that offers a low-friction and wear-resistant interface for weight-bearing surface articulation in diarthrodial joints, but it lacks vascularity. It displays an inherent inability to heal when injured in a skeletally mature individual. Joint-preserving treatment procedures such as mosaicplasty, débridement, perichondrium transplantation and autologous chondrocyte implantation have shown variable results, and the average long-term result is sub-standard. Because of these limitations of the treatment methods and lack of intrinsic repair capacity of mature cartilage tissue, an alternative treatment approach is needed, and synovial mesenchymal stromal cells (SMSCs) represent an attractive therapeutic alternative because of their ex vivo proliferation capacity, multipotency and ability to undergo chondrogenesis.
  
  
  METHODS
  SMSCs were isolated from tissues obtained by arthroscopy using two types of biopsies. Ex vivo cell expansion was accomplished under static and dynamic culture followed by characterization of cells according to the International Society for Cellular Therapy guidelines. Kinetic growth models and metabolite analysis were used for understanding the growth profile of these cells.
  
  
  RESULTS
  For the first time, SMSCs were expanded in stirred bioreactors and achieved higher cell density in a shorter period of time compared with static culture or with other mesenchymal stromal cell sources.
  
  
  CONCLUSIONS
  In this study we were able to achieve (8.8 ± 0.2) × 10(5) cells within <2 weeks in dynamic culture under complete xeno-free conditions. Our results also provided evidence that after dynamic culture these cells had an up-regulation of chondrogenic genes, which can be a potential factor for articular cartilage regeneration in clinical settings.
authors.affiliation: Department of Bioengineering and Institute for Biotechnology and Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Aruna
authors.initials: A
authors.lastname: Santhagunam
authors.affiliation: Department of Bioengineering and Institute for Biotechnology and Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Dos Santos
authors.affiliation: Department of Bioengineering and Institute for Biotechnology and Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Madeira
authors.affiliation: Centro Hospitalar de Lisboa Ocidental, E.P.E, Hospital São Francisco Xavier, Lisboa, Portugal.
authors.forename: João B
authors.initials: JB
authors.lastname: Salgueiro
authors.affiliation: Department of Bioengineering and Institute for Biotechnology and Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal. Electronic address: joaquim.cabral@ist.utl.pt.
authors.forename: Joaquim M S
authors.initials: JM
authors.lastname: Cabral
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D020219:Chondrogenesis / Q000235:genetics*; D006801:Humans; D051457:Hyaline Cartilage / Q000166:cytology* / Q000254:growth & development; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology; D013582:Synovial Fluid / Q000166:cytology*; D059467:Transcriptome
keywords: articular cartilage; chondrogenic differentiation; micro-based dynamic culture; synovial mesenchymal stromal cells