Microfluidic Organotypic Model for Monocyte Transendothelial Migration to the Joint in Obese Osteoarthritic Patients

I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio88 enrolled

Overview

Osteoarthritis (OA) is the fastest growing cause of disability worldwide due to population ageing and increasing obesity incidence. Obese individuals have a higher risk of OA insurgence and severe progression due to several risk factors, including their systemic inflammation state and superior migratory ability of monocytes. In the present project we aim at the development of a novel 3D microfluidic organotypic model resembling the joint to investigate the migration ability of monocytes from obese and non-obese OA patients. We hypothesize that monocytes from obese OA patients display superior migration ability and a specific pattern of chemokine surface receptors compared to monocytes from non-obese OA patients. We also hypothesize that these features lead to a superior infiltration of monocytes/macrophages to the synovial membrane in obese OA patients. Based on this, our main aim will be to highlight differences between Mo from obese and non-obese OA patients in terms of surface receptors and migration ability in a microfluidic organotypic model.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Osteoarthritis

Interventions

use of patient-derived biological samplesOTHER

We will use biological samples that are routinely collected as waste material from patients undergoing prosthetic surgery at IRCCS Istituto Ortopedico Galeazzi. Peripheral blood will be also collected from patients during the pre-surgery visit and during the post-surgery hospitalization coinciding with routine blood sample collection.

Eligibility

Sex: ALLMin age: 60 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion criteria Obese OA patients * Subscription of informed consent * BMI ≥ 30 * age between 60-80 years included * Kelgrenn-Lawrence equal or superior to grade III * presence of synovitis * patients undergoing knee replacement * suspension of NSAIDs from one week before the surgical procedure according to the standard clinical practice Non-obese OA patients * Subscription of informed consent * BMI ≤ 28 * age between 60-80 years included * Kelgrenn-Lawrence equal or superior to grade III * presence of synovitis * patients undergoing knee replacement * suspension of NSAIDs from one week before the surgical procedure according to the standard clinical practice Exclusion criteria Obese OA patients - HCV, HIV, HBV, TPHA infection Non-obese OA patients \- HCV, HIV, HBV, TPHA infection

Outcomes

Primary Outcomes

Chemokine receptor expression

To evaluate and compare the expression of chemokine surface receptors on monocytes from obese and non-obese OA patients.

Time frame: 24 hours

Secondary Outcomes

Monocyte transendothelial migration

To monitor the transendothelial migration of monocytes from OA patients in response to chemokines present in the synovial fluid using a microfluidic organotypic model.

Time frame: 48 hours