Meniscus injuries, the most common intra-articular knee injury, can result in severe pain and disability. Current treatments for these matrix-abundant tissues, such as arthroscopic repairs or meniscectomies, often result in post-traumatic injuries throughout surrounding tissues and increased risk of osteoarthritis. Tissue regeneration-based repair is an ideal route to treating injuries and maintaining the function of these vital connective tissues. Critical to this goal is defining functional cell subpopulations in the meniscus, as the current consensus identifies meniscal fibrochondrocytes as col1/col2 co-expressing cells. Specifically, there is an urgent need to identify matrix-producing cells, analyze their potential for repairing injured tissue, and define their corresponding biomarkers’ biological functions.

To address this gap, we are performing single-cell RNA sequencing (scRNAseq) and subsequent genomic analysis on pediatric meniscus tissues. Our analysis has revealed differential expression of genes related to matrix production and organization within distinct cell subpopulations. These subpopulations yielded a novel characterization of human meniscal fibrochondrocytes which distinguished cells that differentially express either collagen 1, representing fibroblast-like cells, or collagen 2, representing chondrocyte-like cells. Several of the key genes within these matrix-producing populations are not yet well-characterized in the meniscus and other human connective tissues. Ongoing work is focused on investigating the functions of these genes and characterizing the phenotypes of the matrix-producing cell subpopulations in different environments. Ultimately, we hope to identify controllable factors that will support regeneration-based treatments for injured meniscus tissues.