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Open AccessReview

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

Regenerative Medicine Technologies Laboratory, Ente Ospedaliero Cantonale (EOC), Via Tesserete 46, 6900 Lugano, Switzerland
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza dell’ Ateneo Nuovo 1, 20126 Milano, Italy
Applied and Translational Research center (ATRc), IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy
Center of Experimental Orthopaedics, Saarland University Medical Center, 66421 Homburg, Germany
Cell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, via Galeazzi, 4, 20161 Milan, Italy
Orthopaedic and Traumatology Unit, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale, Via Tesserete 46, 6900 Lugano, Switzerland
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(11), 1867;
Received: 13 September 2019 / Revised: 16 October 2019 / Accepted: 23 October 2019 / Published: 4 November 2019
(This article belongs to the Special Issue Cartilage Repair and Restorative Procedures)
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. View Full-Text
Keywords: Exosome; extracellular vesicles; mesenchymal stem cell; knee osteoarthritis; injection Exosome; extracellular vesicles; mesenchymal stem cell; knee osteoarthritis; injection
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D’Arrigo, D.; Roffi, A.; Cucchiarini, M.; Moretti, M.; Candrian, C.; Filardo, G. Secretome and Extracellular Vesicles as New Biological Therapies for Knee Osteoarthritis: A Systematic Review. J. Clin. Med. 2019, 8, 1867.

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