Table 4.
Summary of the immunomodulatory potential of MSC-EVs.
| Target cells | Experimental approach | Source of EVs and isolation method | Results | Reference |
|---|---|---|---|---|
| PBMC | In vitro coculture | Human umbilical cord MSC | ↓ Proliferation of CD8+ and CD4+ | (99) |
| UC (Sed.: 10,000 × g) and Exoquick | ↑ Percentage of CD4+CD25+FoxP3+ Tregs | |||
| ↑ TGF-β1 and IL-10; ↓ IFN-γ, IL-6, TNF-α | ||||
| Colon cells | TNBS-induced colitis model | Human BM-MSCs | ↓ Pro-inflammatory cytokine levels in injured colons | (261) |
| UC (Sed.: 100,000 × g) | Suppression of apoptosis | |||
| Inhibition of NF-kBp65 signal transduction pathways | ||||
| T lymphocytes | In vitro coculture | Human ASCs | Decreased T-cell activation and proliferation | (97) |
| UC (Sed.: 100,000 × g) | ||||
| Auto-reactive lymphocytes | EAE mice | Murine BM-MSCs | EVs express PD-L1, galectin-1, and TGF-β1 | (96) |
| UC (Sed.: 100,000 × g) | Inhibition auto-reactive T-cell responses | |||
| ↑ Apoptosis | ||||
| ↑ CD4+CD25+FoxP3+ Tregs | ||||
| PBMC from type I diabetes patients | In vitro coculture | Human BM-MSC | ↓ IFN-γ production and ↑ TGF-β, IL-10, IL-6, and PGE2 | (98) |
| UC (Sed.: 100,000 × g) | ↓ Level of Th17 cells and ↑ FoxP3+ Tregs | |||
| B lymphocytes | In vitro coculture | Human BM-MSC | Inhibition of B-cell proliferation and differentiation | (95) |
| UC (Sed.: 100,000 × g) and UF | ||||
| THP-1 MФ | In vitro coculture and in vivo injection of EVs in a mouse model of allogeneic skin grafting | Human ESC-MSC | ↑ Anti-inflammatory cytokines | (100) |
| HPLC | ↓ Pro-inflammatory cytokines | |||
| TLR-dependent induction of M2-like phenotype | ||||
| Treg cell expansion | ||||
| In vitro coculture | LPS treated UC-MSC | MФ polarization via delivery of Let-7b by EVs and inhibition of TLR4 signaling pathway | (84) | |
| UC (Sed.: 100,000 × g) | ||||
| moDCs from type I diabetic patients | In vitro coculture | Human BM-MSC | EV-conditioned DCs exhibited immature phenotype | (101) |
| UC (Sed.: 100,000 × g) | ↑ IL-10, IL-6, and TGFβ | |||
| ↓ IL-17 and Th17 cells | ||||
| Treg expansion |
Sed., sedimentation rate; UC, ultracentrifugation; UF, ultrafiltration; Tregs, regulatory T cells; EAE, experimental autoimmune encephalomyelitis; TNBS, 2,4,6 trinitrobenzene sulfonic acid; HPLC, high performance liquid chromatography; BM-MSC, bone marrow-derived MSC; ASC, adipocyte-derived stem cells; NF-kBp65, nuclear Factor kappa B p65; TGF-β1, transforming growth factor beta 1; IL-10, interleukin 10; IFN-γ, interferon gamma; IL-6, interleukin 6; TNF-α, tumor necrosis factor alpha; PD-L1, programed death ligand 1; PGE2, prostaglandin E2; TLR, toll-like receptor; IL-17, interleukin 17; Th, T-helper cell; MФ, macrophage; moDCs, monocyte-derived dendritic cells; LPS, lipopolysaccharide; FoxP3, forkhead box P3.