Podium Presentation Osteoarthritis

12.2.4 - Extracellular Vesicles Derived From Mesenchymal Stromal Cells Cultured in a Clinical-Grade Edium Promote Human Cartilage Recovery.

Presentation Topic
Osteoarthritis
Date
13.04.2022
Lecture Time
16:48 - 16:57
Room
Potsdam 3
Session Type
Free Papers
Speaker
  • C. Gentili (Genoa, IT)
Authors
  • C. Gentili (Genoa, IT)
  • M. Palamà (Genoa, IT)
  • G. Shaw (Galway, IE)
  • F. Barry (Galway, IE)
  • M. Murphy (Galway, IE)
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Osteoarthritis (OA) is a joint disorder causing articular cartilage degeneration. Currently, treatments are mainly pain- and symptom-modifying, rather than disease-modifying. Human bone marrow stromal cells (hBMSCs) have emerged as a promising paracrine mechanism-based approach for the treatment of OA. Many studies demonstrate that MSCs attend to tissue repair through the secretion of trophic factors or extracellular vesicles (EVs). We developed a “donor-to-patient” system for aseptic therapeutic cell manufacturing using a xeno-free medium. We validated the potential therapeutic benefits of secreted EVs isolated from BMSC culture in this innovative culture system, for cartilage repair.

Methods and Materials

We characterized (EVs) derived from hBMSCs, grown in a xeno-free culture system (XFS) compared to a conventional fetal bovine serum (FBS) culture system, in normoxic and hypoxic culture setting. We investigated also the therapeutic potential of EVs in an in vitro model of OA. We characterized the miRNA content of EVs in different culture setting to select putative miRNA that could be involved in a biological function.

Results

The biological effects of XFS- and FBS-cultured hBMSC-derived EVs were tested on IL-1α treated hACs in an experiment designed to mimic the OA environment. We observed that under inflammatory conditions hACs are able to recruit and internalize more MSC-derived EVs, especially those derived from cells cultured in our XFS system and in hypoxic conditions. XFS-EVs both in normoxia and hypoxia shows anti-inflammatory properties in an in vitro OA model. Analysis of miRNA content showed upregulation in XFS-hBMSC-derived EVs of miRNAs known to have a chondroprotective role, and also appear to be involved in cartilage homeostasis and influence TGF-beta signaling.

Conclusion

XFS medium was found to be suitable for isolation and expansion of hBMSCs with increased production of EVs. The application of these EVs overcomes the safety concerns associated with serum-containing media and makes ready-to-use clinical cartilage therapies more accessible.

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