Synovium-Derived and Bone-Derived Mesenchymal Stem/Stromal Cells from Early OA Patients Show Comparable In Vitro Properties to Those of Non-OA Patients

Abstract

Degenerative disorders like osteoarthritis (OA) might impair the ability of tissue-resident mesenchymal stem/stromal cells (MSCs) for tissue regeneration. As primary cells with MSC-like properties are exploited for patient-derived stem cell therapies, a detailed evaluation of their in vitro properties is needed. Here, we aimed to compare synovium-derived and bone-derived MSCs in early hip OA with those of patients without OA (non-OA). Tissues from three synovial sites of the hip (paralabral synovium, cotyloid fossa, inner surface of peripheral capsule) were collected along with peripheral trabecular bone from 16 patients undergoing hip arthroscopy (8 early OA and 8 non-OA patients). Primary cells isolated from tissues were compared using detailed in vitro analyses. Gene expression profiling was performed for the skeletal stem cell markers podoplanin (PDPN), CD73, CD164 and CD146 as well as for immune-related molecules to assess their immunomodulatory potential. Synovium-derived and bone-derived MSCs from early OA patients showed comparable clonogenicity, cumulative population doublings, osteogenic, adipogenic and chondrogenic potential, and immunophenotype to those of non-OA patients. High PDPN/low CD146 profile (reminiscent of skeletal stem cells) was identified mainly for non-OA MSCs, while low PDPN/high CD146 mainly defined early OA MSCs. These data suggest that MSCs from early OA patients are not affected by degenerative changes in the hip. Moreover, the synovium represents an alternative source of MSCs for patient-derived stem cell therapies, which is comparable to bone. The expression profile reminiscent of skeletal stem cells suggests the combination of low PDPN and high CD146 as potential biomarkers in early OA.