title: In-vitro chondrogenic potential of synovial stem cells and chondrocytes allocated for autologous chondrocyte implantation - a comparison : Synovial stem cells as an alternative cell source for autologous chondrocyte implantation.
abstract: OBJECTIVE
  The use of passaged chondrocytes is the current standard for autologous chondrocyte implantation (ACI). De-differentiation due to amplification and donor site morbidity are known drawbacks highlighting the need for alternative cell sources.
  
  
  METHODS
  Via clinically validated flow cytometry analysis, we compared the expression of human stem cell and cartilage markers (collagen type 2 (Col2), aggrecan (ACAN), CD44) of chondrocytes (CHDR), passaged chondrocytes for ACI (CellGenix™), bone marrow derived mesenchymal stem cells (BMSC), and synovial derived stem cells (SDSC).
  
  
  RESULTS
  Primary, human BMSC and SDSC revealed similar adipogenic, osteogenic, and chondrogenic differentiation potential and stem cell marker expression. However, the expression of the chondrogenic markers Col2 and ACAN was statistically significant higher in SDSC. CHDR and SDSC expressed ACAN and CD44 equally, but Col2 was expressed more strongly on the SDSC surface. The marker expression of SDSC from osteoarthritic joints (Kellgren-Lawrence score ≥3) versus normal knees (Kellgren-Lawrence score ≤2) did not differ. Similarly, there was no difference between temporarily frozen and fresh SDSC. Col2 and ACAN surface expression declined with further passaging, whereas CD44 remained unchanged. We observed the same effect after reducing the serum content. When comparing CHDR for ACI with SDSC of the same passage (P2/3), both Col2 and ACAN, correlating with clinical outcome, were expressed higher in SDSC.
  
  
  CONCLUSIONS
  In summary, SDSC demonstrated high differentiation potential and a stable chondrogenic phenotype. They might therefore be better suitable for ACI than BMSC or passaged CHDR.
authors.affiliation: Department of Orthopaedics and Trauma Surgery, Medical Center, Faculty of Medicine, - Albert-Ludwigs-University of Freiburg, Freiburg, Germany. johanna.kubosch@uniklinik-freiburg.de.
authors.forename: Eva Johanna
authors.identifier: http://orcid.org/0000-0001-9460-3520
authors.initials: EJ
authors.lastname: Kubosch
authors.affiliation: Department of Orthopaedics and Trauma Surgery, Medical Center, Faculty of Medicine, - Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Heidt
authors.affiliation: Department of Orthopaedics and Trauma Surgery, Medical Center, Faculty of Medicine, - Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Niemeyer
authors.affiliation: Department of Orthopaedics and Trauma Surgery, Medical Center, Faculty of Medicine, - Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Bernstein
authors.affiliation: Department of Orthopaedics and Trauma Surgery, Medical Center, Faculty of Medicine, - Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
authors.forename: Norbert P
authors.initials: NP
authors.lastname: Südkamp
authors.affiliation: Department of Orthopaedics and Traumatology, Odense University Hospital, Odense, Denmark.|Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Hagen
authors.initials: H
authors.lastname: Schmal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053674:Aggrecans / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis; D024043:Collagen Type II / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008875:Middle Aged; D019637:Orthopedic Procedures; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000601:surgery; D010012:Osteogenesis; D013234:Stem Cells / Q000378:metabolism*; D000070918:Synoviocytes / Q000378:metabolism*; D014182:Transplantation, Autologous / Q000379:methods*
chemical_list: D053674:Aggrecans; C497483:CD44 protein, human; D024043:Collagen Type II; D018960:Hyaluronan Receptors
keywords: Autologous chondrocyte implantation; Cartilage repair; Cell quality; Collagen type II