Table 1.
The Biological Effects and Mechanisms of MSCs and MSC-Evs in AD
| Source | MSC/MSC-Evs | Target Cells | Mechanism | Outcomes/Effects | Ref. |
|---|---|---|---|---|---|
| Human umbilical cord | MSC-Exs | T cells | Downregulation of IFN-γ and IL-17 in T cells; inhibition of T cell activation |
Significantly decreased clinical symptom score, serum IgE level, and histological dermatitis score | [55] |
| Human adipose tissue | MSCs | T cells | Suppressed expression of MIP-2; inhibited miR-122a-5p-SOCS1 axis; Th1/Th2 regulation | Reduced clinical symptoms; reduced number of degranulated mast cells; decreased IgE levels, histamine release, and PGE2 | [56] |
| Human adipose tissue | MSCs | T cells | Downregulation of IL-4R expression; suppressed Th2 inflammation; regulation of PD-L1, TGF-β and PGE2; inhibition of Th17 cells activation and IL-17 expression | Ameliorated ova-induced AD symptoms | [57] |
| Mice bone marrow | MSCs | B cells | Inhibition of Blimp-1 expression; inhibition of the terminal differentiation of B cells | Regulation of B cell differentiation | [58] |
| Human adipose tissue | MSCs | B cells | Inhibition of COX-2 signaling pathway; reduced maturation and proliferation of B cells; increased TGF-β secretion | Alleviating AD symptoms; regulating B cell function | [59] |
| Human umbilical cord | MSCs | B cells | Increased level of TGF-β; inhibition of B cell maturation and IgE secretion | Improved symptoms in AD mice | [60] |
| Human tonsils | MSC-Evs | Mast cells | Regulation of inflammation in mast cells; targeting of miRNAs in Evs | Inhibiting the activation and proliferation of mast cells | [61] |
| Human umbilical cord | MSCs | Mast cells | Regulation PGE2 via NOD2-RIP2-COX-2 signaling pathway; affecting TGF-β1 via IL-4-STAT6 signaling pathway; inhibiting the degranulation of mast cells | Significantly improved the symptoms of AD; reducing the clinical severity and epidermal hyperplasia in mice | [62] |
| Human bone marrow | MSCs | HUVECs | Increased expression of VEGF and Ang2; promoting angiogenesis | Promoting wound healing | [63] |
| The Wharton’s jelly tissue | MSCs | HUVECs | Upregulation of VEGF, EGF, bFGF, and KDR expression; promoting neoangiogenesis | Alleviating radiation-induced skin injury in rats | [64] |
| Human cord blood | MSCs | Keratinocytes | Promoting the differentiation into keratinocytes | Improving wound healing of skin defects in mice | [65] |
| Human cord blood | MSC-Evs | HSFs and HMECs | Induction of PTEN and SPRY1 of PI3K/Akt and ERK1/2 pathway activation by miR-21-3p | Accelerating re-epithelialization; reducing scar width; promoting fibroblast proliferation, migration, and angiogenesis; promoting skin wound healing | [66] |
| Human umbilical cord | MSC-Evs | HaCAT and DFL | Activation of the AKT pathway; inhibition of skin cell apoptosis; activation of Wnt4/β-catenin and AKT signaling | Promoting skin repair in second-degree burn injury | [67] |
Abbreviations: AD, Atopic dermatitis; MSCs, mesenchymal stem cells; HUVECs, Human umbilical vein endothelial cells; HSFs, Human skin fibroblasts; HMECs, Human microvascular endothelial cells; HaCAT, human immortalized keratinocytes; DFL, Dermal fibroblasts; TGF-β1 Transforming growth factor-βl; IFN-γ, Interferon gamma; IL-17, interleukin 17; MIP-2, macrophage inflammatory protein 2; SOCS1, suppressor of cytokine signaling 1; Mast cells, Mast cells; Th1, T helper 1; Th2, T helper 2; IL-4R, Interleukin-4 Receptors; PD-L1, Programmed Death-Ligand 1; PGE2, Prostaglandin 2; Th17 cells, T helper 17 cells; COX-2, cyclooxygenase-2; miRNA, MicroRNA; NOD2, Nucleotide-binding oligomerization domain 2; RIP2, receptor-interacting protein 2; COX-2, Cyclooxygenase-2; IL-4, Interleukin-4; VEGF, Vascular Endothelial Growth Factor; Ang2, Angiopoietin-2; EGF, Epidermal Growth Factor; bFGF, basic fibroblast growth factor; KDR, Vascular Endothelial Growth Factor Receptor; BMSCs, bone marrow mesenchymal stem cells; UC-MSCs, umbilical cord mesenchymal stem cells; MSC-Exs; MSC extracts; AdMSCs, Adipose mesenchymal stem cell; ova, ovalbumin; hAT-MSCs, Human adipose tissue mesenchymal stem cell; hub-MSCs, Human umbilical cord mesenchymal stem cells; IgE, Immunoglobulin E; T-MSC-Evs, tonsils mesenchymal stem cell extracellular vesicles; PTEN, phosphatase and tensin homolog; SPRY1, sprouty homolog 1; PI3K/Akt pathway, Phosphatidylinositol 3-kinase protein kinase b pathway; ERK1/2 pathway, extracellular regulated protein kinases pathway; Akt pathway, protein kinase b pathway; Wnt4/β-catenin, Wnt4/β-catenin Pathway.