Potential Mechanism of Action of Current Point-of-Care Autologous Therapy Treatments for Osteoarthritis of the Knee-A Narrative Review

Abstract

Osteoarthritis (OA) is a progressive degenerative disease that manifests as pain and inflammation and often results in total joint replacement. There is significant interest in understanding how intra-articular injections made from autologous blood or bone marrow could alleviate symptoms and potentially intervene in the progression of the disease. There is in vitro an in vivo evidence that suggests that these therapies, including platelet-rich plasma (PRP), autologous anti-inflammatories (AAIs), and concentrated bone marrow aspirate (cBMA), can interrupt cartilage matrix degradation driven by pro-inflammatory cytokines. This review analyzes the evidence for and against inclusion of white blood cells, the potential role of platelets, and the less studied potential role of blood plasma when combining these components to create an autologous point-of-care therapy to treat OA. There has been significant focus on the differences between the various autologous therapies. However, evidence suggests that there may be more in common between groups and perhaps we should be thinking of these therapies on a spectrum of the same technology, each providing significant levels of anti-inflammatory cytokines that can be antagonists against the inflammatory cytokines driving OA symptoms and progression. While clinical data have demonstrated symptom alleviation, more studies will need to be conducted to determine whether these preclinical disease-modifying findings translate into clinical practice.

Keywords: autologous anti-inflammatory; concentrated bone marrow aspirate; intra-articular injection; mechanism of action; osteoarthritis; platelet-rich plasma.

Figure 1

Model of feed-forward loop of pro-inflammatory cytokine-driven OA progression. IL-1β and TNFα bind to chondrocytes and induce expression of MMP-13. MMP-13 causes cartilage matrix breakdown. Cartilage breakdown products inflame cells in the synovium, inducing more production of IL-1β and TNFα.

Figure 2

Cytokine contribution from components of blood used to make autologous therapies.

Figure 3

Correlation of WOMAC pain score and ratio of IL-1ra:IL-1β injection in OA subjects [34,47].