Estandarización del plasma rico en plaquetas como medicamento para la artrosis

Abstract

Osteoarthritis (OA) is the most frequent joint pathology (it affects 15% of world population), disabling and of uncertain etiology. Low-grade chronic inflammation has a fundamental role in its development and progression and culminates in the imbalance between the anabolism and the catabolism of articular cartilage, which has a poor regeneration capacity. Platelet rich plasma (PRP) is an autologous product with therapeutic potential, but its clinical efficacy for OA has not been conclusively proved. This is mainly due to the lack of standardization of preparation methods, the consequent heterogeneity in the resulting PRP derivatives and, as a result, the disparity in both preclinical and clinical results. The objective of this Doctoral Thesis was to standardize PRP lysates based on defined absolute platelet concentrations and, thus, a composition independent from the basal platelet concentration of the donor. Its potential application in three relevant indications for OA was tested by means of in vitro models with mesenchymal stromal cells (MSCs) or OA chondrocytes (from knee or hip). The evaluated applications were: 1. Intraarticular therapy with chondrogenic properties. 2. Tridimensional scaffold for the regeneration of cartilage injuries. 3. Intraarticular anti-inflammatory therapy. The results of our models showed that PRP derivatives in lysate form do not only lack chondrogenic capacity, but also inhibit it and, conversely, promote the differentiation to the osteogenic lineage, independently of platelet dose. Instead, when MSCs are embedded in the fibrin gels resulting from PRPs activation, the increase in platelet concentration is beneficial. On the other hand, anti-catabolic, anti-oxidant and anti-inflammatory effects were proved when using platelet concentrations much lower than physiological values. Conversely, platelet enrichment was pro-inflammatory, especially in hip OA chondrocytes. These molecular results were further corroborated in a 21-day ex vivo model with OA cartilage. In conclusion, this study proposed an innovative standardization methodology for the preparation of PRP, based in absolute platelet concentration, and showed that the standardization of PRP products is essential to objectively evaluate its effects. As far as we know, this is also the first study that separately compares the effects of PRPs on knee and hip chondrocytes.