Immunomodulation via paracrine signaling by mesenchymal stem cell secretome

Immunomodulation via paracrine signaling by mesenchymal stem/stromal cells describes the ability of MSCs to influence immune cell function and tissue homeostasis by secreting a diverse array of soluble factors and extracellular vesicles (the secretome). These paracrine signals can suppress pro-inflammatory cytokine production, induce anti-inflammatory cell phenotypes (such as M2 macrophages and regulatory T cells), promote tissue repair, and affect angiogenesis. This mode of action is central to the therapeutic rationale for using MSCs or their secretome in immune-mediated and degenerative diseases. The process is mediated by the concerted action of cytokines (e.g., IL-10, prostaglandin E2), enzymes (e.g., indoleamine 2,3-dioxygenase), growth factors, and regulatory non-coding RNAs delivered via exosomes. Notably, this is not a classical “target” suitable for small molecule drugs, but an entire networked mechanism of mediators.

Other names

MSC secretome-mediated immunomodulationMSC paracrine immunomodulationMesenchymal stromal cell paracrine effects

The mechanism involves the suppression of pro-inflammatory cytokines (e.g., TNF-α, IL-6) and secretion of anti-inflammatory mediators (e.g., prostaglandin E2, IL-10, indoleamine 2,3-dioxygenase). It also includes the induction of macrophage polarization toward anti-inflammatory phenotypes (M2), stimulation of regulatory T cell (Treg) induction, and transfer of regulatory miRNAs via extracellular vesicles.