Repair of chronic osteochondral defects using predifferentiated mesenchymal stem cells in an ovine model

Matthias Zscharnack, Pierre Hepp, Robert Richter, Thomas Aigner, Ronny Schulz, Jeremy Somerson, Christoph Josten, Augustinus Bader, Bastian Marquass

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Background: The use of mesenchymal stem cells (MSCs) to treat osteochondral defects caused by sports injuries or disease is of particular interest. However, there is a lack of studies in large-animal models examining the benefits of chondrogenic predifferentiation in vitro for repair of chronic osteochondral defects. Hypothesis: Chondrogenic in vitro predifferentiation of autologous MSCs embedded in a collagen I hydrogel currently in clinical trial use for matrix-associated autologous chondrocyte transplantation facilitates the regeneration of a chronic osteochondral defect in an ovine stifle joint. Study Design: Controlled laboratory study. Methods: The optimal predifferentiation period of ovine MSCs within the type I collagen hydrogel in vitro was defined by assessment of several cellular and molecular biological parameters. For the animal study, osteochondral lesions (diameter 7 mm) were created at the medial femoral condyles of the hind legs in 10 merino sheep. To achieve a chronic defect model, implantation of the ovine MSCs/ hydrogel constructs was not performed until 6 weeks after defect creation. The 40 defects were divided into 4 treatment groups: (1) chondrogenically predifferentiated ovine MSC/hydrogel constructs (preMSC-gels), (2) undifferentiated ovine MSC/hydrogel constructs (unMSC-gels), (3) cell-free collagen hydrogels (CF-gels), and (4) untreated controls (UCs). Evaluation followed after 6 months. Results: With regard to proteoglycan content, cell count, gel contraction, apoptosis, compressive properties, and progress of chondrogenic differentiation, a differentiation period of 14 days in vitro was considered optimal. After 6 months in vivo, the defects treated with preMSC-gels showed significantly better histologic scores with morphologic characteristics of hyaline cartilage such as columnarization and presence of collagen type II. Conclusion: Matrix-associated autologous chondrocyte transplantation with predifferentiated MSCs may be a promising approach for repair of focal, chronic osteochondral defects. Clinical Relevance: The results suggest an encouraging method for future treatment of focal osteochondral defects to prevent progression to osteoarthritis.

Original languageEnglish (US)
Pages (from-to)1857-1869
Number of pages13
JournalAmerican Journal of Sports Medicine
Volume38
Issue number9
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

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Keywords

  • Chondrogenic predifferentiation
  • Chronic
  • Mesenchymal stem cells
  • Osteochondral defect
  • Sheep

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Zscharnack, M., Hepp, P., Richter, R., Aigner, T., Schulz, R., Somerson, J., Josten, C., Bader, A., & Marquass, B. (2010). Repair of chronic osteochondral defects using predifferentiated mesenchymal stem cells in an ovine model. American Journal of Sports Medicine, 38(9), 1857-1869. https://doi.org/10.1177/0363546510365296