Effect of Combined Intraosseous and Intraarticular Infiltrations of Autologous Platelet-Rich Plasma on Subchondral Bone Marrow Mesenchymal Stromal Cells from Patients with Hip Osteoarthritis

Abstract

Osteoarthritis (OA) is a debilitating condition that significantly impacts its patients and is closely associated with advancing age and senescence. Treatment with autologous platelet rich plasma (PRP) is a novel approach that is increasingly being researched for its effects. Subchondral bone mesenchymal stromal cells (MSCs) are key progenitors that form bone and cartilage lineages that are affected in OA. This study investigated the changes in subchondral bone MSCs before and after combined intraosseous (IO) and intraarticular (IA) PRP infiltration. Patient bone marrow aspirates were collected from 12 patients (four male, eight female) aged 40–86 years old (median 59.5). MSCs were expanded in standard media containing human serum to passage 1 and analysed for their colony-forming potential, senescence status, and gene expression. Hip dysfunction and Osteoarthritis Outcome Score (HOOS) at baseline and 6 months post second infiltration were used to assess the clinical outcomes; seven patients were considered responders and five non-responders. The number of colony-forming MSCs did not increase in the post treatment group, however, they demonstrated significantly higher colony areas (14.5% higher compared to Pre) indicative of enhanced proliferative capacity, especially in older donors (28.2% higher). Senescence assays also suggest that older patients and responders had a higher resistance to senescent cell accumulation. Responder and non-responder MSCs tended to differ in the expression of genes associated with bone formation and cartilage turnover including osteoblast markers, matrix metalloproteinases, and their inhibitors. Taken together, our data show that in hip OA patients, combined IO and IA PRP infiltrations enhanced subchondral MSC proliferative and stress-resistance capacities, particularly in older patients. Future investigation of the potential anti-ageing effect of PRP infiltrations and the use of next-generation sequencing would contribute towards better understanding of the molecular mechanisms associated with OA in MSCs.

The Combined Intraosseous Administration of Orthobiologics Outperformed Isolated Intra-articular Injections in Alleviating Pain and Cartilage Degeneration in a Rat Model of MIA-Induced Knee Osteoarthritis

“…The role and mechanisms of subchondral bone marrow lesions in OA progression have been gradually clarified. In vivo studies targeting subchondral bone lesions have shown that IO infiltrations of PRP can rescue synovial fluid 33 and bone marrow–derived mesenchymal stem cells (MSCs) 19 from senescence, restore their cellular potential, enhance their osteogenesis, and protect against oxidative stress. Despite limited clinical evidence, early studies have shown promising results regarding the effectiveness of IO PRP injections for OA treatment.…”

Intra-osseous plasma rich in growth factors enhances cartilage and subchondral bone regeneration in rabbits with acute full thickness chondral defects: Histological assessment

“…The IO infiltration with PRGF might enhance the performance of the SB by inducing the influx of additional MSCs, that help to maintain tissue homeostasis, thus diminishing the activation of proinflammatory cytokines preventing further cartilage loss. Moreover, Ganguly et al ( 33 ) have recently investigated the changes in SB MSCs before and after combined IA and IO infiltrations of PRP in patients with hip OA. Their data showed that combined IO and IA infiltrations of this biological therapy, enhanced SB MSCs proliferative and stress-resistance capacities ( 33 ).…”

“…Moreover, Ganguly et al ( 33 ) have recently investigated the changes in SB MSCs before and after combined IA and IO infiltrations of PRP in patients with hip OA. Their data showed that combined IO and IA infiltrations of this biological therapy, enhanced SB MSCs proliferative and stress-resistance capacities ( 33 ). This could be another reason why the IO infiltration of PRGF provides a greater regeneration of the SB and the AC in rabbits with full depth chondral defects.…”

“…Combining intra-osseous (IO) and IA PRP injections to target SB can provide a more complete treatment by stimulating biological processes that lead to a homeostatic environment in the whole joint, which also influences the behavior of MSCs that coordinate SB and AC remodeling ( 32 , 33 ). Various research groups have already showed that the IO approach is safe and provides longer-term functional and clinical benefits compared to IA injections of PRP alone ( 34 – 37 ).…”

Anti-Aging Potential of Platelet Rich Plasma (PRP): Evidence from Osteoarthritis (OA) and Applications in Senescence and Inflammaging

“…MSCs from older OA patients had a higher increase in their proliferative capacity. They also demonstrated higher protection from oxidative stress as indicated by senescence assay [ 32 ]. Reported investigations of the anti-inflammatory potential of PRP [ 33 ] and the use of PRP to combat senescence [ 34 , 35 ] further indicate the potential of PRP in use beyond OA in other ARDs for tissue regeneration.…”