Human Cartilage-Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears.

Meniscus 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.

Effects of Tranexamic Acid Cytotoxicity on In Vitro Chondrocytes.

Use of topical tranexamic acid (TXA) in orthopedic surgery has been expanding over the past decade, with increasing evidence confirming reductions in perioperative blood loss and transfusion requirements, but there is minimal evidence regarding effects of TXA on native cartilage. We conducted a study to understand the in vitro effects of TXA on bovine cartilage and murine chondrocytes and ultimately to expand the clinical application of topical TXA to include scenarios with retained native cartilage, such as hemiarthroplasty. Bovine cartilage explants were exposed to TXA at a concentration of 100 mg/mL, and glycosaminoglycan (GAG) release and cell viability were measured at 8, 24, and 48 hours. Monolayer murine chondrocytes were exposed to TXA 25, 50, and 100 mg/mL, and viability was measured at 8, 24, and 48 hours. GAG released from bovine explants was significantly higher in the samples exposed to TXA 100 mg/mL at all time points. Cell viability was significantly decreased in the explants exposed to TXA 24 and 48 hours after initial incubation. Bovine chondrocyte viability was not affected by TXA 25 mg/mL. Murine chondrocyte viability was similar between the TXA 25 mg/mL and control samples at all time points. The TXA 50 mg/mL sample dropped from 66.51% viability at 8 hours to 6.81% viability at 24 hours and complete cell death by 48 hours. The TXA 100 mg/mL samples had no observable viable cells at 8, 24, and 48 hours. Our data indicated that TXA 100 mg/mL damaged and was cytotoxic to bovine explanted cartilage and was cytotoxic to murine chondrocytes. Murine and bovine chondrocyte viability were not affected by TXA 25 mg/mL.