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.

Highlights

  • Osteoarthritis (OA) is a degenerative disease with progressive degradation of articular cartilage and subchondral bone leading to loss of joint function and pain which significantly impairs patient quality of life [1,2]

  • 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

  • Mesenchymal stem cells (MSCs) represent the most promising cell population [8,9] showing, in several clinical studies, the possibility to increase joint function and reduce pain in knee OA patients [10–12]. The efficacy of this cell injection approach may be impaired by cell manipulation, and its wide application is strongly limited by regulatory issues [13,14]

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Summary

Introduction

Osteoarthritis (OA) is a degenerative disease with progressive degradation of articular cartilage and subchondral bone leading to loss of joint function and pain which significantly impairs patient quality of life [1,2]. Worldwide estimates indicate that 9.6% of men and 18.0% of women over 60 years old suffer from symptoms of OA, with knee OA representing one of the most disabling conditions, with a huge social impact [3–5]. This high prevalence of OA is further increasing due to the augmented risk of OA due both to non-modifiable risk factors, such as the aging population and the gender, and to local risk factors, such as physical activity [6]. Mesenchymal stem cells (MSCs) represent the most promising cell population [8,9] showing, in several clinical studies, the possibility to increase joint function and reduce pain in knee OA patients [10–12]. The efficacy of this cell injection approach may be impaired by cell manipulation, and its wide application is strongly limited by regulatory issues [13,14]

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