Background/Purpose: , The discovery of MSCs in the synovium and synovial fluid (SF) provided a potential mechanism for repairing cartilage “from the top down”. Indeed, we have shown in a canine model that MSCs injection into synovial fluid in canine OA is associated with MSC adhesion to damaged cartilage which may potentially contribute to subsequent joint repair (Baboolal T et al ARD 2015). Moreover, it is possible that SF-MSCs may be lost under joint irrigation at arthroscopic procedures. The purpose of this work was threefold; first to test the hypothesis that SF-MSCs can be replaced, and also their numbers further increased by synovial agitation, second that these cells were capable of rapid adhesion to clots and third that the clot composition improve MSC migration.

Methods: , Initially, ex-vivo mechanical agitation of both excised porcine and human synovium was tested using a panel of cytology brushes and custom made prototypes. Based on the prototype devices a “synovial brush” for human in vivo intra-operative MSC release in patients undergoing arthroscopy was developed and compared to a conventional cytology brush. Colony-forming unit-fibroblast (CFU-F) assay was performed to quantify released MSCs. Adhesion to clots was studied by comparing Platelet Rich Plasma (PRP), Whole Blood (WB) and Fibrin Glue (FG) to evaluate the effect of this adjunctive therapies on MSC function. Migration studies were performed using passage 2-4 synovial MSCs in trans-well migration assay. MSC migration, over a five hour period, was compared between PRP and pooled human Platelet Lysate (hPL). The functional integrity of brushed MSCs was confirmed using trilineage assays for bone, fat and cartilage differentiation.

Results: Ex-vivo mechanical agitating of the synovium with the cytology brush compared to irrigation alone increased MSC number 2.7-fold (n=10, p=0.002). Based on in vitro studies, we selected a custom designed synovial brush for in vivo studies in patients and compared to the cytology brush, the custom designed brush resulted in a median 65-fold increase in the number of CFU-Fs (n=8, p=0.0148). Trilineage differentiation of released synovial MSCs was at least comparable to donor match synovial fluid MSCs. We also noted that existing standard arthroscopic procedures with irrigation during arthroscopy effectively removed the majority of CFU-Fs from the joint cavity. Released synovial MSCs adhered to clots within 30 minutes with no difference seen between clot compositions. These MSCs demonstrated a trend for a better migration towards hPL compared to PRP.

Conclusion: Conventional arthroscopy procedures wash away SF-MSCs. Using a novel brushing technique and a custom designed synovial brush, synovial MSCs can be mechanically released in vivo, and these cells were capable of rapid migration and adhesion and had excellent preservation of chondrogenesis. Collectively these findings show that endogenous minimally manipulated MSCs can be readily increased, and provide a one-stage procedure combining synovial brushing with arthroscopy towards a low cost simple procedure in developing endogenous MSCs for joint repair in OA. This knowledge may aid in the development of a Rheumatological medical arthroscopy strategy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-novel-one-stage-technique-applicable-during-arthroscopy-for-the-mobilization-of-synovial-mesenchymal-stromal-cells-towards-joint-regeneration/