Table 7.

Summary of relevant preclinical studies in rodents intended to improve the therapeutic efficacy by MSC preconditioning.

Disease Entity	Experimental Lung Disease Model	Cell Source	MSC Modification	MSC Species	Dose (Cells)	Application Route	Time Point of Application	Repeated Application	Biological Function In Vivo	Molecular Changes/Results	Reference
ALI	endotoxin	BM	hypoxia	human	5 × 104 cells/g	i.v.	n.a.	no	ischemic preconditioning potentiates the protective effect of through the secretion of exosome	less neutrophil influx and pro-inflammatory cytokine dysbalance with upregulation of IL-10	[74]
ALI	CLP	BM	preconditioning with carbon monoxide	mice	5 × 105(2 h) 2.5 × 105 (24 h/48 h)	i.v.	2 h, 24 h, 48 h p.i.	yes	increased survival and alleviated lung injury	preconditioning stipulates the production of proresolving lipid mediators, especially resolvins	[166]
ALI	E. coli	BM	MSC pretreatment with Toll-like receptor-3 agonist	human	2 × 107 vs. 4 × 107	i.v.	1 h p.i.	no	reduced pulmonary edema and bacterial load	increased antimicrobial activity of macrophages after application of pretreated EV	[167]
asthma	dust mite	BM	pretreatment of MSC with eicosapentaenoic acid	mice	1 × 105	i.t.	1 d a.t.	no	reduced bronchoconstriction and lung tissue remodeling	reduced influx of eosinophils, macrophages, neutrophils and lymphocytes, shift towards anti-inflammatory macrophages and increased release of inflammation resolving and anti-inflammatory mediators	[171]
COPD	elastase, cigarette smoke	AT	preconditioning with pioglitazone	human	1 × 105	i.v.	7 d a.t.	no	more efficient repair of lung injury	increased VEGFA production	[109]
COPD	elastase	AM	MSC predifferentiation to lung epithelial like progenitor cells	mice	1 × 105	i.t.	2 weeks a.t.	no	improved lung regeneration, reduced presence of inflammatory and lung remodeling factors	integration of predifferentiated cells into lung alveolar structures	[168]
IPF	bleomycin	BM	oncostatin M preconditioning	mice	2 × 105	i.t.	3 d a.t.	no	improved attenuation of inflammation, TGF-β1 and OSM induced extracellular matrix production, release of fibrotic factors	upregulation of paracrine HGF	[165]

i.v.—intravenous; i.t.—intratracheal; p.i.—post infection; a.t.—after treatment; MSC—mesenchymal stem cell; ALI—acute lung injury; COPD—chronic obstructive pulmonary disease; IPF—idiopathic pulmonary fibrosis; BM—bone marrow-derived MSC; AT—adipose tissue-derived MSC; AM—amniotic-derived MSC; CLP—cecal ligation and puncture; h—hours; d—day; EV—extracellular vesicles; n.a.—not applicable; IL—interleukin; VEGFA—vascular endothelial growth factor A; HGF—hepatocyte growth factor; TGF-ß1—transforming growth factor beta 1; OSM—oncostatin M.