Table 1.

Therapeutic application of various mesenchymal stem cells and their extracellular vesicles in preclinical COPD and asthma models

Injury	Study type	type of MSCs	Infusion method	Dose of injection	Outcome	Reference
COPD	NCI-H292 airway epithelial cells	TNF-α and IL-1β-activated BM-MSCs	–	–	Increased airway epithelial wound healing via activation of the epidermal growth factor receptor	[48]
COPD	Mice model	BM-MSCs	Intravenous	4 × 106 cells/mL	Relieved lung injury through promoting proliferation of endogenous lung stem cells	[49]
COPD	Rat model	BM-MSCs	Intratracheal	6 × 106 cells/mL	Protect cigarette smoke-damaged lung and pulmonary function partly via VEGF–VEGF receptors	[50]
COPD	Mice model	BM-MSCs	Intravenous	4 × 106 cells/mL	Ameliorate lung injury through anti-inflammatory and anti-bacterial effect	[51]
COPD	Rat model	BM-MSCs	Intratracheal	6 × 106 cells/mL	Alleviated airway inflammation and emphysema through down-regulation of cyclooxygenase-2 via p38 and ERK MAPK pathways	[52]
COPD	Mice model	BM-MSCs	Intravenous	5 × 105 cells/mouse	Exerted HGF dependent cytoprotective effects	[53]
COPD	Rat model	BM-MSCs	Intravenous	2 × 106 cells/rat	Inhibited the progression of emphysema by differentiating into endotheliocytes and suppressing the apoptosis of endotheliocytes and oxidative stress	[54]
COPD	Mice model	HSP-VEGFA-BM-MSCs	Intravenous	–	Alleviated elastase-induced emphysema	[55]
Asthma	Mice model	BM-MSCs	Intravenous	106 cells/mouse	Simvastatin and BM-MSCs combination therapy affects serum IgE as well as lung IL-13 and TGFβ levels more than BM-MSCs and simvastatin therapy alone	[63]
Asthma	Mice model	BM-MSCs	Intravenous	2.5 × 105 cells	Controlled inflammation, immune-inflammatory factors and mitochondrial related genes, and prevent asthma immune-pathology	[64]
			Bronchial	2.5 × 105 cells
Asthma	Mice model	BM-MSCs	Intratracheal	105 cells/mouse	Released different mediators and differentially affected airway and lung parenchyma	[65]
		AD-MSCs
		Lung-MSCs
Asthma	Rat model	BM-MSCs	Intratracheal	2 × 106 cells/rat	CM and especially MSCs ameliorated pathological changes via intratracheal route presumably by targeting ICAM-1 and VCAM-1 in lung tissues	[66]
Asthma	Mice model	BM-MSCs	Intraperitoneal	106 and 2 × 106 cells	Ameliorated to the airway remodeling and airway inflammation both in the upper and lower airways via the inhibition of Th2 immune response in the murine model of AR	[67]
Asthma	Rat model	BM-MSCs	Intravenous	–	Affected on Th1/Th2 drift, and the Notch1/Jagged1 pathway and may participate in the homing of the BM-MSCs	[68]
Asthma	Mice model	BM-MSCs	Intravenous	2 × 106 cells/mouse	Significantly reduced total cells and eosinophilia and serum OVA-specific IgE concentration and inhibited expressions of Th2 and Th17 cytokines and elevated levels of Treg cytokines	[69]
Asthma	Mice model	BM-MSCs	–	–	Alleviated asthma by inducing polarization of alveolar macrophages	[70]
Asthma	Mice model	BM-MSCs	retro-orbital	106 cells/mouse	Participated in improved outcomes of remodeling by reversing excess collagen deposition and changing hyaluronan levels	[71]
COPD	Mice model	ASMCs-treated iPSC-MSCs	Intravenous	106 cells/mouse	Alleviated oxidative stress-induced mitochondrial dysfunction in the airways	[72]
Asthma	Mice model	iPSC-MSCs mesenchymoangioblast-MSCs	Intranasal	106 cells/mouse	Provided greater protection against experimental chronic allergic airways disease compared with a clinically used corticosteroid	[73]
COPD	Mice model	Pioglitazone pretreated WJ-MSCs	Intravenous	104 cells/mouse	Produced greater lung regeneration, compared to non-augmented WJ-MSCs, in a mouse emphysema model	[74]
COPD	Mice model	WJ-MSCs	Intravenous	5 × 104 cells/mouse	They didn’t confirm the effects of WJ-MSCs in COPD through this experiment	[75]
COPD	Mice model	HCB-MSCs	Intravenous	5 × 104 cells/mouse	Improved the regenerative mechanisms based on the gene expression profile changes	[76]
Asthma	Mice model	HCB-MSCs	Intravenous	105 cells/mouse	Suppressed severe asthma by directly regulating Th2 cells and type 2 innate lymphoid cells	[77]
Asthma	Mice model	AD-MSCs BM-MSCs	Intravenous	2.5 × 107 cells/Kg	Suppressed AHR and airway inflammation and induced eosinophilic airway inflammation and lung histological changes	[81]
Asthma	Mice model	AD-MSCs	Intratracheal	106 cells/mouse	Alleviated airway inflammation, improved airway remodeling, and relieved AHR	[17]
Asthma	Mice model	AD-MSCs	Intravenous	105 cells/mouse	Reduced lung inflammation and remodeling while causing immunosuppression	[82]
Asthma	Feline model	AD-MSCs	Intravenous	2 × 106, 4 × 106, 4.7 × 106 and 107 cells/cat	Had a delayed potential in decreasing airway inflammation, AHR and remodeling	[83]
Asthma	Mice model	HAM-MSC-CM	Intravenous	106 cells/mouse	Reduced inflammatory factors and fibrosis	[84]
Asthma	Rat model	HP-MSCs	Intraperitoneal	106 cells/Kg	Suppressed airway inflammation in asthmatic rats by modulating Notch signaling	[85]
Asthma	In vitro	HP-MSCs	–	–	Reduced the IL-5 level experimentally in children with asthma	[86]
Asthma	Rat model	HP-MSCs	Intravenous	1 × 107 cells/ml	Improved AHR and inflammation by modulating the Th17/Treg balance	[87]
Asthma	In vitro	DF-MSCs	–	–	Down-regulated Th2-mediated immune response in asthmatic patients mononuclear cells	[88]
COPD	Mice model	BM-MSCs and BM-MSC-Exos	Intraperitoneal	106 cells	Combination treatment may act against early events caused by CS exposure owing to its anti-inflammatory and other mitochondrial transfer mechanisms	[89]
Asthma	In vitro	BM-MSC-Exos	–	–	Promoted immunosuppression of regulatory T cells	[90]
Asthma	Rat model	BM-MSCs and BM-MSC-Exos	Intravenous	5 × 106 cells/cat	Reduced airway remodeling in lungs through the Wnt/β-catenin signaling pathway	[91]
Asthma	Mice model	BM-MSC-Exo-miR-188	–	–	Reduced bronchial smooth muscle cell proliferation in asthma through suppressing the JARID2/Wnt/β-catenin axis	[92]
Asthma	In vitro	BM-MSC-Exo-miR-146a-5p	–	–	Inhibited Th2 differentiation via regulating miR-146a-5p/SERPINB2 pathway	[93]
Asthma	Mice model	AD-MSC-EVs	Intranasal	10 μg	Alleviated AHR and allergic airway inflammation caused by the induction of Treg expansion	[94]
Asthma	Mice model	AD-MSC-Exo-miR-301a-3p	–	–	Regulated airway smooth muscle cells by targeting STAT3	[95]
Asthma	Mice model	AD-MSC-EVs	Jugular	37 μg	Acted differentially on lung mechanics and inflammation in experimental allergic asthma	[96]
Asthma	Mice model	mmu_circ_0001359-modified AD-MSC-Exos	Intravenous	200 μg	Attenuated airway remodeling by enhancing FoxO1signaling-mediated M2-like macrophage activation	[97]
Asthma	Mice model	iPSC-MSC- EV-miR-146a-5p	Intravenous	100 µg	Prevented group 2 innate lymphoid cell-dominant allergic airway inflammation	[98]
Asthma	Mice model	Hypoxic-hUC-MSC-EVs	Intravenous	40 μg	Attenuated allergic airway inflammation and airway remodeling	[99]
Asthma	RAW 264.7 cell line	HUC-MSC-Exos	–	–	Attenuated the inflammation of severe steroid-resistant asthma by reshaping macrophage polarization	[100]
COPD	Mice model	P-MSC-Exo-MAPPS	–	–	Enhanced pulmonary function through decreasing serum concentrations of inflammatory cytokines, lung-infiltrated macrophages, neutrophils, and natural killer and antigen-presenting cells and elevated anti-inflammatory IL-10 and (Tregs)	[101]
Asthma	Mice model	hP-MSC-Exos	Intranasal	50 μg	Expanded lung IL-10-producing IMs, which may originate from spleen, thus contribute to protection against asthma	[102]