Autologous mesenchymal stem cells or meniscal cells: what is the best cell source for regenerative meniscus treatment in an early osteoarthritis situation?

Abstract

BackgroundTreatment of meniscus tears within the avascular region represents a significant challenge, particularly in a situation of early osteoarthritis. Cell-based tissue engineering approaches have shown promising results. However, studies have not found a consensus on the appropriate autologous cell source in a clinical situation, specifically in a challenging degenerative environment. The present study sought to evaluate the appropriate cell source for autologous meniscal repair in a demanding setting of early osteoarthritis.MethodsA rabbit model was used to test autologous meniscal repair. Bone marrow and medial menisci were harvested 4 weeks prior to surgery. Bone marrow-derived mesenchymal stem cells (MSCs) and meniscal cells were isolated, expanded, and seeded onto collagen-hyaluronan scaffolds before implantation. A punch defect model was performed on the lateral meniscus and then a cell-seeded scaffold was press-fit into the defect. Following 6 or 12 weeks, gross joint morphology and OARSI grade were assessed, and menisci were harvested for macroscopic, histological, and immunohistochemical evaluation using a validated meniscus scoring system. In conjunction, human meniscal cells isolated from non-repairable bucket handle tears and human MSCs were expanded and, using the pellet culture model, assessed for their meniscus-like potential in a translational setting through collagen type I and II immunostaining, collagen type II enzyme-linked immunosorbent assay (ELISA), and gene expression analysis.ResultsAfter resections of the medial menisci, all knees showed early osteoarthritic changes (average OARSI grade 3.1). However, successful repair of meniscus punch defects was performed using either meniscal cells or MSCs. Gross joint assessment demonstrated donor site morbidity for meniscal cell treatment. Furthermore, human MSCs had significantly increased collagen type II gene expression and production compared to meniscal cells (p < 0.05).ConclusionsThe regenerative potential of the meniscus by an autologous cell-based tissue engineering approach was shown even in a challenging setting of early osteoarthritis. Autologous MSCs and meniscal cells were found to have improved meniscal healing in an animal model, thus demonstrating their feasibility in a clinical setting. However, donor site morbidity, reduced availability, and reduced chondrogenic differentiation of human meniscal cells from debris of meniscal tears favors autologous MSCs for clinical use for cell-based meniscus regeneration.

Single-cell RNA-seq analysis identifies meniscus progenitors and reveals the progression of meniscus degeneration

“…An increasing number of studies are supporting the idea that cell-based strategies effectively improve meniscus repair and regeneration 32 33. However, it is still not clear which cell type is most effective for meniscus repair 34 35. Recently, meniscus stem/progenitor cells have been considered as the most suitable cell type for meniscus injury repair due to them having the same tissue origin and histocompatibility,36 37 however, the characteristics, marker genes and isolation methods of human meniscus progenitor cells have not yet been fully elucidated.…”

The role of meniscal repair for prevention of early onset of osteoarthritis

“…Long-term data of the prevention of osteoarthritis by meniscus reconstruction are also missing for animal models. However the resection of meniscal tissue leads to cartilage lesions and degenerative changes of the knee after a very short time (Zellner et al, 2017 ).…”

The Meniscus Tear: A Review of Stem Cell Therapies

“…Several scaffolds have been developed ranging from synthetic polymers to more natural tissue-derived sources. In vitro studies have demonstrated the outcomes of using different cell types [7] and the benefits of adding growth factors to cultures that can promote GAG production and improve cell differentiation enhancing the bioactivity of the overall scaffold for integration [95]. Such study models have also shed light on the effects of inhibitory effects on the meniscal repair by interleukin-1 and tumor necrosis factor-α commonly upregulated in injured joints [96][97][98].…”

“…Owing to the complex phenotype of meniscal tissue, tissue regeneration using stem cell therapy may hold the key to tackling meniscal tears. The use of both meniscal cells and mesenchymal stem cells (MSCs) have proven effective in regenerating meniscal tissue, however meniscal cell harvest poses an unacceptable donor site morbidity and tear site cells have little to no chondrogenic potential [7]. Therefore, the majority of research has been focused on stem cells where there is a reasonable amount of pre-clinical data but limited clinical data.…”