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

Study Overview
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Brief Summary
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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.

Official Title
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Development of a Microfluidic Organotypic Model to Evaluate Monocyte Transendothelial Migration to the Joint in Obese Osteoarthritic Patients

Conditions
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Osteoarthritis

Intervention / Treatment
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* Other: use of patient-derived biological samples


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| obese OA patients<br>Use of patient-derived biological samples Inclusion Criteria: 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 Exclusion criteria: - HCV, HIV, HBV, TPHA infection | Other: use of patient-derived biological samples<br>* 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.<br>|
| Non-obese OA patients<br>Use of patient-derived biological samples Inclusion criteria: 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: - HCV, HIV, HBV, TPHA infection | Other: use of patient-derived biological samples<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chemokine receptor expression | To evaluate and compare the expression of chemokine surface receptors on monocytes from obese and non-obese OA patients. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 48 hours |