Browsing by Subject "Meniscus"
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Item Open Access Human Cartilage-Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears.(Stem cells (Dayton, Ohio), 2019-01) Jayasuriya, Chathuraka T; Twomey-Kozak, John; Newberry, Jake; Desai, Salomi; Feltman, Peter; Franco, Jonathan R; Li, Neill; Terek, Richard; Ehrlich, Michael G; Owens, Brett DMeniscus injuries are among the most common orthopedic injuries. Tears in the inner one-third of the meniscus heal poorly and present a significant clinical challenge. In this study, we hypothesized that progenitor cells from healthy human articular cartilage (chondroprogenitor cells [C-PCs]) may be more suitable than bone-marrow mesenchymal stem cells (BM-MSCs) to mediate bridging and reintegration of fibrocartilage tissue tears in meniscus. C-PCs were isolated from healthy human articular cartilage based on their expression of mesenchymal stem/progenitor marker activated leukocyte cell adhesion molecule (ALCAM) (CD166). Our findings revealed that healthy human C-PCs are CD166+, CD90+, CD54+, CD106- cells with multilineage differentiation potential, and elevated basal expression of chondrogenesis marker SOX-9. We show that, similar to BM-MSCs, C-PCs are responsive to the chemokine stromal cell-derived factor-1 (SDF-1) and they can successfully migrate to the area of meniscal tissue damage promoting collagen bridging across inner meniscal tears. In contrast to BM-MSCs, C-PCs maintained reduced expression of cellular hypertrophy marker collagen X in monolayer culture and in an explant organ culture model of meniscus repair. Treatment of C-PCs with SDF-1/CXCR4 pathway inhibitor AMD3100 disrupted cell localization to area of injury and prevented meniscus tissue bridging thereby indicating that the SDF-1/CXCR4 axis is an important mediator of this repair process. This study suggests that C-PCs from healthy human cartilage may potentially be a useful tool for fibrocartilage tissue repair/regeneration because they resist cellular hypertrophy and mobilize in response to chemokine signaling. Stem Cells 2019;37:102-114.Item Open Access Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries.(Arthritis research & therapy, 2021-11) Kim-Wang, Sophia Y; Holt, Abigail G; McGowan, Alyssa M; Danyluk, Stephanie T; Goode, Adam P; Lau, Brian C; Toth, Alison P; Wittstein, Jocelyn R; DeFrate, Louis E; Yi, John S; McNulty, Amy LBackground
Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries.Methods
Twenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects.Results
Using the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type.Conclusions
Our findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury.Item Open Access The Meniscus Cell Phenotype: Effects of Physical, Mechanical, and Inflammatory Environments(2022) Andress, BenjaminThe meniscus of the knee is a fibrocartilaginous structure essential to the biomechanical integrity and function of the knee joint. Millions of people suffer meniscus injuries each year, and meniscus tears are common at all ages and stages of life. Meniscus injury has long-term consequences: loss of meniscus function has been definitively linked to early-onset osteoarthritis. Treatment options for meniscus injury remain limited; although there has been a recent movement to surgically repair the meniscus whenever possible, partial meniscectomy remains one of the most commonly performed orthopedic surgeries. Due to this urgent need, there is currently great interest in methods to stimulate meniscus healing, augment repair, and improve long-term outcomes following meniscus injury using pharmaceutical, biological, or tissue engineering methods. Research on meniscus regenerative medicine, however, is greatly limited by a lack of understanding of meniscus cellular biology.In this dissertation, this gap in knowledge is addressed with a thorough characterization of the meniscus cell phenotype. We have investigated the phenotypic identity of meniscus cells from inner and outer zones of the meniscus by RNA-sequencing, and provide comparisons to articular cartilage and isolated, monolayer cultured meniscus cells. We found that in situ meniscus cells from both the inner and outer zones are strikingly distinct from either articular chondrocytes or monolayer expanded meniscus cells at the transcriptomic level, and that inner and outer zone meniscus cells may be more similar to each other than to chondrocytes or monolayer cultured cells. Differences were also observed between inner and outer zone cells, and this dataset provides a wealth of novel targets for characterizing inner and outer zone cells to better understand regional cell biology of the meniscus. We investigated the role of the physical microenvironment, including native extracellular matrix, monolayer culture, and biomaterial hydrogels, to modulate the meniscus cell transcriptional phenotype and support meniscus cell culture and expansion in vitro. Our findings provide new details on the meniscus cell dedifferentiation process, and demonstrate the utility of bioengineered hydrogels to reverse meniscus cell dedifferentiation for long-term in vitro culture. We also investigated the effect of an injury-relevant inflammatory stimulus (IL-1), and the potential for dynamic mechanical loading to modulate the inflammatory response of meniscus cells in two models of dynamic physiologic loading, cell stretch of isolated meniscus cells and compression of tissue explants. Results of RNA-sequencing, gene set enrichment analysis, and RT-qPCR from both models showed significant modulation of inflammation-related genes and pathways with mechanical stimulation, supporting the potential of mechanotransduction pathways as novel therapeutic targets to improve outcomes following meniscus injury. Overall, this work provides a wealth of data characterizing the meniscus cell phenotype and lays the groundwork for future studies of meniscus regenerative medicine and tissue engineering. Furthermore, this work entailed considerable development and validation of methods for in vitro studies of meniscus cell biology and mechanotransduction, which will be valuable to the field of meniscus research. The work presented in this dissertation represents an enormous step forward in understanding the effects of physical, mechanical, and inflammatory environments on the meniscus cell phenotype, which is essential to the development of effective novel therapies to stimulate meniscus repair and prevent PTOA.