Abstract

Objective: Mesenchymal stromal cells (MSCs) can be used intra-articularly to quell inflammation and promote cartilage healing; however, mechanisms by which MSCs mitigate joint disease remain poorly understood. Galectins, a family of β-galactoside binding proteins, regulate inflammation, adhesion and cell migration in diverse cell types. Galectin-1 and galectin-3 are proposed to be important intra-articular modulators of inflammation in both osteoarthritis and rheumatoid arthritis. Dose warping following deformable image registration (DIR) has been proposed for interfractional dose accumulation. Robust evaluation workflows are vital to clinically implement such procedures. Dose distributions were then calculated on each artificially deformed image and warped back to the original anatomy following DIR by a commercial algorithm. Spatial registration was evaluated by quantitative comparison of the original and warped structure sets, using conformity index and mean distance to conformity (MDC) metrics. BMSCs constitutively express high levels of galectin-1 mRNA relative to other articular cell types, suggesting a possible mechanism for their intra-articular immunomodulatory properties. BMSC galectin expression and motility are impaired in an inflammatory environment, which may limit tissue repair properties following intra-articular administration. β-lactose-mediated galectin inhibition also impaired BMSC adhesion and motility. Dosimetric evaluation was performed by quantitative comparison of the dose-volume histograms generated for the calculated and warped dose distributions, which should be identical for the ideal “perfect” registration of mass-conserving deformations.This study demonstrates a workflow for validation of dose warping following DIR that could assist physicists and physicians in quantifying the the effects of joint inflammation on BMSC function and the potential therapeutic effects of BMSC galectin expression in OA uncertainties associated with dose accumulation in clinical scenarios.