Secretome and Extracellular Vesicles as New Biological Therapies for Knee Osteoarthritis: A Systematic Review

Abstract

Secretome and extracellular vesicles (EVs) are considered a promising option to exploit mesenchymal stem cells’ (MSCs) properties to address knee osteoarthritis (OA). The aim of this systematic review was to analyze both the in vitro and in vivo literature, in order to understand the potential of secretome and EVs as a minimally invasive injective biological approach. A systematic review of the literature was performed on PubMed, Embase, and Web of Science databases up to 31 August 2019. Twenty studies were analyzed; nine in vitro, nine in vitro and in vivo, and two in vivo. The analysis showed an increasing interest in this emerging field, with overall positive findings. Promising in vitro results were documented in terms of enhanced cell proliferation, reduction of inflammation, and down-regulation of catabolic pathways while promoting anabolic processes. The positive in vitro findings were confirmed in vivo, with studies showing positive effects on cartilage, subchondral bone, and synovial tissues in both OA and osteochondral models. However, several aspects remain to be clarified, such as the different effects induced by EVs and secretome, which is the most suitable cell source and production protocol, and the identification of patients who may benefit more from this new biological approach for knee OA treatment.

Secreted Factors and EV-miRNAs Orchestrate the Healing Capacity of Adipose Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis

“…Although it is quite well-accepted that MSCs act through paracrine mechanisms on resident cells, nevertheless, a thorough characterization of soluble factors and EV content is lacking and would be essential to define MSCs and MSC-enriched products. In this perspective, in the last years, researchers have tried to couple the array of secreted molecules with the observed protective effects in clinical experiences [58,59]. Despite valuable hints, very often, the input datasets had two major flaws.…”

Characterization and Chondroprotective Effects of Extracellular Vesicles From Plasma- and Serum-Based Autologous Blood-Derived Products for Osteoarthritis Therapy

“…Current research on regenerative approaches for cartilage recovery focuses on EVs derived from mesenchymal stem/stromal cells (MSCs) obtained from adipose tissue (A-MSC), bone marrow (BM-MSCs), or embryonic stem cells (ESC-MSCs) (D'Arrigo et al, 2019;Li et al, 2019). EVs from A-MSCs were shown to increase cartilage matrix synthesis indicated by type II collagen (COL2A1) expression and reduced expression of catabolic enzymes such as matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) in OA chondrocytes (Wu et al, 2019), while reducing inflammation via promoting transition to the M2 phenotype of macrophages (Lo Sicco et al, 2017).…”

Bone marrow concentrate injections for the treatment of osteoarthritis: evidence from preclinical findings to the clinical application

“…Only few preclinical studies focused on the intraarticular injective use of BMAC for OA, while the majority of these studies focused on culture-expanded BMSCs or on surgical applications of BMAC, including the treatment of focal cartilage defects (surgical augmentation or scaffoldbased applications) [14,70,71]. The few preclinical studies in the literature suggested that BMAC can affect OA progression in the animal models, but they also underlined its limited potential, and the possibility to further exploit it through different production protocols as well as the combination of injective carriers to positively affect cell migration and favor longer-lasting homeostatic and disease-modifying effects [51,72].…”