Development of an organotypic microfluidic model to reproduce monocyte extravasation process in the osteoarthritic joint

Abstract

p¼0.0014, respectively) (Fig 1A). Receiver operating characteristics (ROC) analysis of SF TGF-b1 (adjusting for age, BMI, gender, baseline OST and JSN) for the determination of any knee OA progression (either OST, JSN or TKR progression vs. non-progression) yielded an area under the curve (AUC) of 0.95 (95% CI [0.87, 0.98]) (Fig 1B). ROC analysis of elastase yielded an AUC of 0.90 (CI [0.80, 0.95]) (Fig 1B). Applying the Youden index as the cutoff value, for TGF-b1 the sensitivity was 97% (CI [89, 99]), the specificity 85% (CI [62, 97]), and the positive predictive value (PPV) 95% (CI [88, 98]). For elastase the sensitivity was 85% (CI [74, 0.92]), the specificity 86% (CI [65, 97]), and the PPV 95% (CI [86, 98]). Conclusions: We have identified activated macrophages and neutrophils as the functional folate receptor bearing cells in knee OA. The correlation of SF TGF-b1 and elastase with the EC20 imaging phenotype confirmed the pro-inflammatory nature of the FRþ cells in vivo. We further confirmed the pro-inflammatory nature of these cells based on the association of these cell markers with knee OA progression. Taken together, these results suggest that these cells could be potential therapeutic targets in OA. The promising AUC scores for these markers also suggest that SF TGF-b1 and elastase could be the novel biomarkers of risk of progression in knee OA.

A Roadmap of In Vitro Models in Osteoarthritis: A Focus on Their Biological Relevance in Regenerative Medicine

“…In this light, this system may provide enormous prospects for having preliminary data on the efficacy of injective treatments; with important perspectives in cartilage repair [ 207 ]. To gain more insights on the role of immune-mediated reactions in OA, Mondadori, C. et al have recently proposed a microfluidic model simulating the monocyte extravasation from the bloodstream to the synovium [ 208 ]. This microfluidic chip contains two micro-chambers with chondrocytes and synovial fibroblasts in fibrin gel, split by a channel matching the synovial fluid.…”

“…When referring to 3D models with scaffolds, their selection covers great importance, since findings vary greatly based on their nature and architecture. Indeed, bioreactors and microfluidics systems also contributed to improving current methodological approaches by introducing specific biochemical and mechanical issues in miniaturized systems [ 204 , 205 , 206 , 207 , 208 ]. Along this line, scientists designed and developed accurate in vitro approaches to model the multiple interactions among cells from joint tissues.…”

“…Along this line, scientists designed and developed accurate in vitro approaches to model the multiple interactions among cells from joint tissues. Several authors have recently developed new structures for mimicking the osteochondral unit and proposed models for the extravasation of monocytes from the peripheral blood exploiting microfluidics [ 19 , 20 , 208 ]. However, several limitations still exist to improve in vitro reliable OA models.…”

Degenerative disease‐on‐a‐chip: Developing microfluidic models for rapid availability of newer therapies

“…[110] Such micro-tissue constructs have potential ability to mimic the cross talk between different cell under mechanical stress and further better understand pathophysiology and inflammatory con- respectively. [111] This structure was assessed for permeability of FITCdextran demonstrating integrity of endothelial monolayer.…”

“…Articular chondrocytes and synovial fibroblasts, obtained from biopsies of OA patients, were cultured in fibrin gel within the cartilage and synovium compartments, respectively. [ 111 ] This structure was assessed for permeability of FITC‐dextran demonstrating integrity of endothelial monolayer.…”