Unraveling the therapeutic effects of mesenchymal stem cells in asthma

Mirershadi, Fatemeh; Ahmadi, Mahdi; Rezabakhsh, Aysa; Rajabi, Hadi; Rahbarghazi, Reza; Keyhanmanesh, Rana

doi:10.1186/s13287-020-01921-2

Stem Cell Research & Therapy

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]

ND, non-determined; “↑”, increase; “↓”, decrease; “→”, ineffective

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ISSN: 1757-6512

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