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Preconditioned mesenchymal stem cells (cMSCs) are an enhanced cell therapy product derived from human mesenchymal stem cells (typically adipose-derived) that have undergone an *in vitro* priming process to augment their immunomodulatory and therapeutic efficacy. In the specific protocol described by researchers at INSERM and Sorbonne Universités, MSCs are "licensed" through a three-day coculture with allogeneic peripheral blood mononuclear cells (PBMCs). This preconditioning step significantly improves the cells' ability to treat autoimmune conditions, such as Myasthenia Gravis, compared to resting MSCs (rMSCs). The therapeutic effect is mediated through multiple pathways, including the inhibition of T and B cell proliferation, the downregulation of proinflammatory cytokines and B-cell activating factors (TNF-α, BAFF), the modulation of costimulatory molecules (CD40, CD40L), and the upregulation of the complement regulator DAF (CD55), which protects the neuromuscular junction from autoantibody-mediated damage.
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