Batch variability and anti-inflammatory effects of iPSC-derived mesenchymal stromal cell extracellular vesicles in osteoarthritis <i>in vitro</i> model

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) hold promise as a cell-free therapy for osteoarthritis (OA), due to their immunomodulatory and anti-inflammatory properties. However, the need for large-scale expansion to obtain MSC-EVs for clinical use can lead to senescence-related changes and loss of stem-like properties. In this scenario, induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) offer the unique opportunity to address obstacles associated with traditional MSC-based therapies. This study used a xeno-free (XFS) medium for long-term expansion of both MSCs and iMSCs, and their EVs comparison. Characterization of both cells and EVs was conducted across different passages, and the anti-inflammatory potential of EVs and iEVs was assessed using an in vitro model of osteoarthritis. Long-term expansion of MSCs resulted in cellular senescence and a reduction in trilineage differentiation capacity by passage five, accompanied by diminished anti-inflammatory properties of EVs. On the other hand, iMSCs exhibited batch-to-batch variability in differentiation and EV biological properties. However, the effects of iMSC-EVs were prolonged compared to MSC-EVs, providing a wider window of activity for therapeutic purposes. Despite this, the variability among iMSC batches poses challenges for their reliability in OA treatment. Further work is needed to overcome t

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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