Phenotypic and functional characterisation of ovine mesenchymal stem cells: application to a cartilage defect model

Ann Rheum Dis. 2008 Mar;67(3):288-95. doi: 10.1136/ard.2007.076620. Epub 2007 Jul 20.

Abstract

Background: Multipotent mesenchymal stromal cells (MSC) are of particular interest for their potential clinical use in cartilage engineering, but a consistent model is missing in large animals.

Objective: In the absence of any detailed study reporting a complete characterisation of the mesenchymal cells isolated from sheep bone marrow, we fully characterised adherent stromal cells and developed a pre-clinical model of cartilage engineering by implantation of autologous MSC in the Merinos sheep.

Methods: Ovine MSC (oMSC) were isolated from bone marrow, expanded and further characterised according to the recently proposed definition of the MSC. The experimental model consists of partial-thickness lesions created in the inner part of the patellae of the posterior legs. Lesions were filled with oMSC with or without chitosan, with or without transforming growth factor (TGF)beta-3, in a fibrin clot.

Results: oMSC were shown to display the three main characteristics of MSC: adherence to plastic, phenotypic profile (positive for CD44, CD105, vimentin and negative for CD34 and CD45), and trilineage differentiation potential. We also report two other important functional characteristics of MSC: support of long-term haematopoiesis and immunosuppressive capacity. In vivo, 2 months after implantation the histological analysis revealed chondrocyte-like cells surrounded by a hyaline-like cartilaginous matrix that was integrated to the host cartilage when oMSC were combined with chitosan and TGFbeta-3.

Conclusions: This study provides for the first time a strong characterisation of oMSC and establishes the basis for a model of cartilage engineering in a large animal.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Division
  • Cells, Cultured
  • Chitosan
  • Disease Models, Animal
  • Female
  • Hematopoiesis / physiology
  • Immune Tolerance
  • Immunophenotyping
  • Knee Injuries / pathology
  • Knee Injuries / therapy*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / physiology
  • Patella / injuries*
  • Sheep, Domestic
  • Tissue Engineering / methods
  • Treatment Outcome
  • Wound Healing

Substances

  • Chitosan