Characterization of regional meniscal cell and chondrocyte phenotypes and chondrogenic differentiation with histological analysis in osteoarthritic donor-matched tissues

Jingsong Wang,Karina Wright,Jan Herman Kuiper,Zhanfeng Cui,Sally Roberts,Weiguo Zhang,John Garcia

doi:10.1038/s41598-020-78757-6

Abstract

Meniscus degeneration is closely related to the progression of knee osteoarthritis (OA). However, there is currently a lack of quantitative and objective metrics to assess OA meniscal cell phenotypes. In this study we investigated the phenotypic markers and chondrogenic potency of avascular and vascular meniscal cells and chondrocytes from medial OA knee joints (n = 10). Flow cytometry results showed that a significantly greater percentage of meniscal cells were positive for CD49b, CD49c and CD166 compared to donor-matched chondrocytes after 14 days in monolayer culture. The integrins, CD49b and CD29, were expressed at a significantly higher level on avascular meniscal cells derived from tissues with a more degenerated inner border than non-degenerate menisci, suggesting that the integrin family may play an important role in meniscus OA pathology. Collagen fibres arranged in a “tree-like” formation within the meniscus appeared to have less blood vessels associated with them in the vascular region of the most degenerate menisci, which may indicate that such structures are involved in the pathological process. We have demonstrated that meniscal cells derived from the lateral meniscus in medial OA patients have chondrogenic capacity in vitro and hence could represent a potential cell source to consider for meniscus tissue engineering.

Highlights

Meniscus degeneration is closely related to the progression of knee osteoarthritis (OA)
Degenerative tears of the meniscus have important consequences for cartilage loss, as the tears interfere with converting axial loading into horizontal tensile strain and subsequently increasing contact stress on the articular cartilage[3]. This evidence suggests that pathological changes and extracellular matrix (ECM) degeneration in menisci may play an important role in the disease process of OA
For all three cell types and for all 10 donors at passage 0, the immunopositivity of the mesenchymal stem cells (MSCs) markers CD73, CD90, CD105 was over 95%, which adhered to the International Society for Cellular Therapy (ISCT) criteria; around 25% of these cells were CD14 positive which should be lower than 2% in MSCs18, but is similar to levels we have reported previously in MSCs derived from other musculoskeletal tissues

Summary

Introduction

Meniscus degeneration is closely related to the progression of knee osteoarthritis (OA). The integrins, CD49b and CD29, were expressed at a significantly higher level on avascular meniscal cells derived from tissues with a more degenerated inner border than non-degenerate menisci, suggesting that the integrin family may play an important role in meniscus OA pathology. Degenerative tears of the meniscus have important consequences for cartilage loss, as the tears interfere with converting axial loading into horizontal tensile strain and subsequently increasing contact stress on the articular cartilage[3]. Together, this evidence suggests that pathological changes and extracellular matrix (ECM) degeneration in menisci may play an important role in the disease process of OA. Investigating the surface marker and gene expression profiles of meniscal cells from OA knees could contribute to this knowledge base

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Conclusion