Prediction of the Effect of the Osteoarthritic Joint Microenvironment on Cartilage Repair

M. Neefjes, B.A.C. Housmans, H.M. van Beuningen, E.L. Vitters, G.G.H. van den Akker, T.J.M. Welting, A.P.M. van Caam, P.M. van der Kraan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

Impact statement We describe the development of a novel molecular tool to predict if an osteoarthritis joint microenvironment is permissive for cartilage repair or not. Such a tool is of great importance in determining the success of mesenchymal stromal cell-based cartilage repair strategies.Osteoarthritis (OA) is characterized by progressive articular cartilage loss. Human mesenchymal stromal cells (MSCs) can be used for cartilage repair therapies based on their potential to differentiate into chondrocytes. However, the joint microenvironment is a major determinant of the success of MSC-based cartilage formation. Currently, there is no tool that is able to predict the effect of a patient's OA joint microenvironment on MSC-based cartilage formation. Our goal was to develop a molecular tool that can predict this effect before the start of cartilage repair therapies. Six different promoter reporters (hIL6, hIL8, hADAMTS5, hWISP1, hMMP13, and hADAM28) were generated and evaluated in an immortalized human articular chondrocyte for their responsiveness to an osteoarthritic microenvironment by stimulation with OA synovium-conditioned medium (OAs-cm) obtained from 32 different knee OA patients. To study the effect of this OA microenvironment on MSC-based cartilage formation, MSCs were cultured in a three-dimensional pellet culture model, while stimulated with OAs-cm. Cartilage formation was assessed histologically and by quantifying sulfated glycosaminoglycan (sGAG) production. We confirmed that OAs-cm of different patients had significantly different effects on sGAG production. In addition, significant correlations were obtained between the effect of the OAs-cm on cartilage formation and promoter reporter outcome. Furthermore, we validated the predictive value of measuring two promoter reporters with an independent cohort of OAs-cm and the effect of 87.5% of the OAs-cm on MSC-based cartilage formation could be predicted. Together, we developed a novel tool to predict the effect of the OA joint microenvironment on MSC-based cartilage formation. This is an important first step toward personalized cartilage repair strategies for OA patients.
Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalTissue Engineering
Volume28
Issue number1-2
Early online date16 Aug 2021
DOIs
Publication statusPublished - 1 Jan 2022

Keywords

  • bioassay
  • osteoarthritic microenvironment
  • mesenchymal stromal cells
  • cartilage formation
  • MESENCHYMAL STEM-CELLS
  • CHONDROGENIC DIFFERENTIATION
  • SYNOVIAL-FLUID
  • INHIBIT CHONDROGENESIS
  • MACROPHAGE
  • CYTOKINES
  • TISSUE

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