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Table 1 List of some in vivo and in vitro studies on the effects of stem cells or cell products on experimental induced asthma

From: Unraveling the therapeutic effects of mesenchymal stem cells in asthma

Stem cell type Route of administration Animal model and type of injury Time of study Outcome Ref
Bone marrow-derived c-Kit+ cells Intratracheally Hyperoxia-induced lung injury in rats 15 days Angiogenesis and pro-angiogenic factors ↑, aveolarization↑, apoptosis↓ [17]
Anti-c-Kit siRNA Intravenously OVA-induced allergic asthma in mouse 72 h after siRNA injection Pulmonary infiltration of inflammatory cells (eosinophils and lymphocytes)↓, IL-4 and IL-5↓ [18]
Anti-c-Kit siRNA Intranasal OVA-induced allergic asthma in mouse 72 h after siRNA injection SCF, IL-4, and IL-5↓, eosinophil infiltration↓ [19]
c-Kit+ cells Intratracheally OVA-induced allergic asthma in mouse 10 days Inflammation ↓, airway remodeling, and function↑ [20]
Bone marrow MSCs Intravenously, Intratracheally OVA-induced allergic asthma in mouse More than 10 days Th2 and Th17 cytokines↓, IgE↓, eosinophilia↓ [21]
Bone marrow MSCs and CM Intratracheally OVA-induced allergic asthma in rats 14 days MSC-treated rats: neutrophili and neutrophilia↓, CD3+/CD4+↓, IL-10↑, IL-4↓ [22]
Bone marrow MSCs and CM Intravenously OVA-induced allergic asthma in rats 14 days CD3+/CD4+↑, CD3+/CD8+↓, immune cells infiltration↓ (the therapeutic effects were more higher than CM) [23]
Adipose-derived MSCs Intratracheally OVA-induced allergic asthma in mouse ND Airway responsiveness↓, lymphocytes infiltration↓, lgE, IL-1β ↓, IL-4 ↓, IL-17F↓, IL-10↑, RORγ↑, CD4+CD25+Foxp3 Treg cells↑ [11]
Adipose-derived MSC Intravenously Feline chronic allergic asthma More than 4 months Airway eosinophilia and responsiveness→, bronchial wall thickening ↓ [24]
Bone marrow mononuclear cells Intratracheally OVA-induced allergic asthma in mouse 7 days Alveolar collapse↓; bronchoconstriction↓; fibrosis↓; IL-4, -5, and -13↓; IFN-γ↑; TGF-β↑ [25]
iPSC-derived MSCs Intratracheally OVA-induced allergic asthma in mouse 4 days Connexin 43-mediated mitochondrial transfer↑, epithelial cells death↓ [26]
Human umbilical cord blood-derived MSCs Intravenously OVA-induced allergic asthma in mouse 29–31 days IL-4, IL-5, and IL-13↓; IgE and IgG1↓; bronchial hyper-responsiveness↓; eosinophil infiltration↓ [27]
iPSCs, and mesenchymoangioblast-derived MSCs Intranasal and Intravenously OVA-induced allergic asthma in mouse 14 days TGF-β1↓; airway/lung fibrosis↓; collagen-degrading gelatinase ↑ [28]
Human ESC-MSCs Intravenously OVA-induced allergic asthma in mouse 20 days Th2 cells and eosinophils↓; Treg↑; periodic acid–Schiff positive cells↓; CD4+CD25+FOXP3+ cells↑; IL-4, IL-5, and IL-13↓; Ccl11, Ccl24, Il13, Il33, and Ear11 expression ↓ [29]
Bone marrow, umbilical cord, and adipose-derived MSCs Intravenously OVA-induced allergic asthma in mouse 7–10 days Eosinophil↓; IL-4, IL-5, and IL-13↓; INF-γ↑; IL-10 producing macrophages↑ [30]
MSC-derived exosomes In vitro Target cells: asthmatic peripheral mononuclear cells 24 h IL-10 and TGF-β↑, proliferation of CD4+CD25+FOXP3+ cells↑ [31]
MSCs CM In vitro GM-CSF-induced asthmatic changes in 3 T3 murine airway fibroblast cells 14 days Collagen types I, III↓; hyaluronan↓ [32]
MSCs Retro-orbital OVA-induced allergic asthma in mouse 4 weeks Hyaluronan↓, airway inflammation↓ [32]
Adipose-derived MSCs Intravenously OVA-induced allergic asthma in mouse 12 days IDO, TGF-β, and PGE2↑ (IL-4, IL-5, and IL-13↓); IFN-γ↑; IL-10↑ [33]
Human placenta MSCs Intravenously OVA-induced allergic asthma in rats 22 days Notch3 and delta-4↑; notch-1, -2 and jagged-1↓; IgE, Th2 cytokines↓ [34]
iPSC-derived MSCs Intravenously OVA-induced allergic asthma in mouse 55 days Fibrosis and α-SMA↓, TGF-β1↓, phosphorylated Smad2/3 expression↓ [35]
Adipose tissue MSC-derived extracellular vesicles Intravenously OVA-induced allergic asthma in mouse 7 days TGF-β↓, fibrosis↓, inflammation↓, bronchiolar Siglec-F+ eosinophils↓, eotaxin↓, CD3+ CD4+ cells↓, CD4+CD25+Foxp3+ cells↑ [10]
Bone marrow MSCs Intravenously OVA-induced allergic asthma in mouse 7 days Pulmonary oxidative stress↓, and nitrotyrosine↓ [36]
Adipose-derived MSCs and bone marrow-derived MSCs Intratracheally HDM-induced allergic asthma in mouse 3–7 days Bone marrow MSCs: IL-10↑, the influx of eosinophils and B cells ↓, alveolar macrophage inflammatory response↓, lung function, and remodeling→, adipose-derived MSCs were ineffective [15]
Adipose-derived MSCs Intravenously HDM-induced allergic asthma in mouse 3 days Inflammation↓, Th1 cytokines↓, hyper-responsiveness →, contractile tissue→, cell integration, and differentiation → [37]
Bone marrow-derived MSCs Intravenously HDM-induced allergic asthma in mouse 8–10 days Airway responsiveness↓, bronchial contraction ↓, inhibitory type 2 muscarinic receptor↑, phagocytosis of MSCs by local macrophages, macrophage M2 suppressive phenotype↑ [38]
Human iPSC-MSCs Intravenously Neutrophilic airway inflammation induced by LPS and OVA in mouse 4–48 h Th cells (Th17)↓, Th cells-associated cytokines↓, neutrophilic airway inflammation↓, p-STAT3↓, GATA3↓, RORγt↓, iPSC-MSCs differentiation into Th cells↑ [39]
Adipose-derived MSCs Intravenously HDM-induced allergic asthma in mouse 7 days IL-3 and IL-4↓, BALF CD4+ T cells, and Eosinophils↓, Fibrosis↓, TGF-β↓, α-actin↓ [40]
Bone marrow-derived MSCs Intravenously Aspergillus fumigatus hyphal extract-induced asthma in mouse 76–78 days Th17-mediated airway inflammation↓, T regulatory cells →, airway hyper-responsiveness↓, BALF Th2, and Th17 soluble mediators↓ [41]
  1. ND, non-determined; “↑”, increase; “↓”, decrease; “→”, ineffective