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CELL THERAPIES

Human cell therapies in preclinical and clinical studies of cartilage repair

HUMAN CELL THERAPIES IN PRECLINICAL AND CLINICAL STUDIES OF CARTILAGE REPAIR

Jade Perry, Claire Mennan, Helen McCarthy, Bernhard Tins, Simran Kaur, Paul Jermin and Sally Roberts

Keele University and Versus Arthritis (in collaboration with personnel in Aberdeen & Liverpool Universities)

December 2019 saw the culmination of 3 years’ work on this project by Jade Perry with the successful completion of her PhD. During this project Jade assessed the ability of human umbilical cord mesenchymal stromal/stem cells (MSCs) in two preclinical models of cartilage injury and osteoarthritis; these cells showed promise as a potential allogeneic therapy when the damage was simply a cartilage injury but not so much with severe endstage OA.

Other aspects of Jade’s study related to CT and MRI scans from patients who have been in the clinical trial, ASCOT (Autologous Stem cells, Chondrocytes Or the Two combined). Together with the help of the clinical radiologists, a score has been devised and evaluated for CT scans which are performed much less readily in these patients but which will hopefully provide very interesting data on the bone aspects within the joint and how osteochondral defects will heal in comparison to chondral ones.

Another aspect studied was assessing the actual size of defect to be treated with ACI on MRIs, which are used to help surgeons decide the best course of treatment for patients with articular cartilage (AC) defects or early OA in the knee and to follow NICE guidelines. One of these is that ACI is appropriate for treating defects greater than 2cmin size. Hence an accurate estimate of the area of the defect to be treated is important both clinically and financially (for reimbursement reasons). This thesis delved into the accuracy of pre-operative MR imaging at predicting cartilage defect sizes at the time of surgical intervention post debridement (removal of damaged AC tissue) (Figure 5). Taking the whole abnormal cartilage region into account, rather than just the full thickness component of the AC defect, better estimates the actual defect size for treatment.

 Figure 5: Measurement of the defect on the patella (P; kneecap) seen on an MRI in the red circle (A), can be interpreted as 10.4mm long (B) if just measuring the area where cartilage is missing or 24.5mm (C) if taking into account the abnormal adjacent cartilage and bone which would normally be debrided prior to treatment with ACI. This obviously affects the calculation of the area to be treated. FC: femoral condyle, TP: tibial plateau