, Volume 67, Issue 5, pp 905–919 | Cite as

Xeno-free chondrogenesis of bone marrow mesenchymal stromal cells: towards clinical-grade chondrocyte production

  • Maria Skog
  • Virpi Muhonen
  • Johanna Nystedt
  • Roberto Narcisi
  • Leena-Stiina Kontturi
  • Arto Urtti
  • Matti Korhonen
  • Gerjo J. V. M. van Osch
  • Ilkka Kiviranta
Method in Cell Science


Current cell-based cartilage therapies relay on articular cartilage-derived autologous chondrocytes as a cell source, which possesses disadvantages, such as, donor site morbidity and dedifferentiation of chondrocytes during in vitro expansion. Due to these and other limitations, novel cell sources and production strategies are needed. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are a fascinating alternative, but they are not spontaneously capable of producing hyaline cartilage-like repair tissue in vivo. In vitro pre-differentiation of BM-MSCs could be used to produce chondrocytes for clinical applications. However, clinically compatible defined and xeno-free differentiation protocol is lacking. Hence, this study aimed to develop such chondrogenic differentiation medium for human BM-MSCs. We assessed the feasibility of the medium using three human BM-MSCs donors and validated the method by comparing BM-MSCs to three other cell types holding potential for articular cartilage repair. The effectiveness of the method was compared to conventional serum-free and commercially available chondrogenic differentiation media. The results show that the defined xeno-free differentiation medium is at least as efficient as conventionally used serum-free chondrogenic medium and performed significantly better on all cell types tested compared to the commercially available chondrogenic medium.


Mesenchymal stromal cells Xeno-free Clinical grade Chondrogenesis 



The authors wish to acknowledge the European Science Foundation’s Regenerative Medicine (REMEDIC) activity, the Maud Kuistila Memorial Foundation and the Emil Aaltonen Foundation for their financial support (V.M.). Viikki Doctoral Programme in Molecular Biosciences (VGSB) is acknowledged for financial support (M.S.). The hACs and hES-MPs were kindly provided by Professor Anders Lindahl (Sahlgrenska University Hospital, Gothenburg, Sweden). Hannu Kautiainen, BA, and Salme Järvenpää, MSc, are acknowledged for their valuable contribution for the statistical analysis (MedCare Ltd, Äänekoski, Finland). The authors thank Sirkka Hirschovits-Gerz for excellent technical assistance with BM-MSC culture (Finnish Red Cross Blood Service, Helsinki, Finland).


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Maria Skog
    • 1
    • 2
  • Virpi Muhonen
    • 1
    • 3
  • Johanna Nystedt
    • 4
  • Roberto Narcisi
    • 5
  • Leena-Stiina Kontturi
    • 6
  • Arto Urtti
    • 6
  • Matti Korhonen
    • 4
  • Gerjo J. V. M. van Osch
    • 5
    • 7
  • Ilkka Kiviranta
    • 1
    • 3
  1. 1.Department of Surgery, Institute of Clinical MedicineUniversity of Helsinki, Biomedicum HelsinkiHelsinkiFinland
  2. 2.Division of Biochemistry and Biotechnology, Department of BiosciencesUniversity of HelsinkiHelsinkiFinland
  3. 3.Department of Orthopaedics and TraumatologyHospital District of Helsinki and UusimaaHelsinkiFinland
  4. 4.Advanced Therapies and Product DevelopmentFinnish Red Cross Blood ServiceHelsinkiFinland
  5. 5.Department of Orthopedics, Erasmus MCUniversity Medical CenterRotterdamThe Netherlands
  6. 6.Division of Biopharmacy and Pharmacokinetics, Centre for Drug ResearchUniversity of HelsinkiHelsinkiFinland
  7. 7.Department of Otorhinolaryngology, Erasmus MCUniversity Medical CenterRotterdamThe Netherlands

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