The Secretome Derived From Mesenchymal Stromal Cells Cultured in a Xeno-Free Medium Promotes Human Cartilage Recovery in vitro

Maria Elisabetta Federica Palamà; Georgina Margaret Shaw; Simonetta Carluccio; Daniele Reverberi; Laura Sercia; Luana Persano; Dario Pisignano; Katia Cortese; Francis Peter Barry; Josephine Mary Murphy; Chiara Gentili

doi:10.3389/fbioe.2020.00090

The Secretome Derived From Mesenchymal Stromal Cells Cultured in a Xeno-Free Medium Promotes Human Cartilage Recovery in vitro

Front Bioeng Biotechnol. 2020 Feb 14:8:90. doi: 10.3389/fbioe.2020.00090. eCollection 2020.

Affiliations

¹ Laboratory of Cellular Oncology, Department of Experimental Medicine, University of Genoa, Genoa, Italy.
² Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.
³ U.O. Molecular Pathology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
⁴ Institute of Nanoscience (CNR-NANO), Pisa, Italy.
⁵ Department of Physics, University of Pisa, Pisa, Italy.
⁶ Department of Experimental Medicine, Human Anatomy, University of Genoa, Genoa, Italy.

Abstract

Osteoarthritis (OA) is a disabling joint disorder causing articular cartilage degeneration. Currently, the treatments are mainly aimed to pain and symptoms relief, rather than disease amelioration. Human bone marrow stromal cells (hBMSCs) have emerged as a promising paracrine mechanism-based tool for OA treatment. Here, we investigate the therapeutic potential of conditioned media (CM) and extracellular vesicles (EVs) isolated from hBMSC and grown in a xeno-free culture system (XFS) compared to the conventional fetal bovine serum-culture system (FBS) in an in vitro model of OA. First, we observed that XFS promoted growth and viability of hBMSCs compared to FBS-containing medium while preserving their typical phenotype. The biological effects of the CM derived from hBMSC cultivated in XFS- and FBS-based medium were tested on IL-1α treated human chondrocytes, to mimic the OA enviroment. Treatment with CM derived from XFS-cultured hBMSC inhibited IL-1α-induced expression of IL-6, IL-8, and COX-2 by hACs compared to FBS-based condition. Furthermore, we observed that hBMSCs grown in XFS produced a higher amount of EVs compared to FBS-culture. The hBMSC-EVs not only inhibit the adverse effects of IL-1α-induced inflammation, but play a significant in vitro chondroprotective effect. In conclusion, the XFS medium was found to be suitable for isolation and expansion of hBMSCs with increased safety profile and intended for ready-to-use clinical therapies.

Keywords: extracellular vesicles; inflammation; mesenchymal stromal cells; osteoarthritis; secretome; xeno-free medium.