Table 1 The ways MSCs on the innate immune responses during LI.

ALI

Injected intratracheal with PA in C57BL/6 mice

AMSCs

Increased the phagocytic ability of macrophages;

Reduced white blood cell count

Reduced the bacterial load, inflammation of lung tissue and histopathological damage

Reduced the activation of NLRC4 inflammasome

[97]

ALI

Injected intraperitoneally with LPS in C57BL/6 mice

AMSC-CM activated by flagellin

Induced macrophage polarization to M2 profile

Alleviated the lung exudation; Inhibited inflammatory cell recruitment in lung tissue; Decreased the concentration of inflammatory factors

/

[98]

ALI

Injected intraperitoneally with LPS in BALB/c mice

BMSCs

Induced further macrophage polarization to M2 profile;

Decreased absolute numbers of neutrophils

Inibited Inflammatory and oxidative stress reaction

Activated STC2/Nrf2 pathway

[31]

ALI

Injected intraperitoneally with CEES in C57BL/6 mice

AMSCs

Prevented the differentiation of CEES-stimulated macrophages into M1 phenotype and stimulated the polarization to M2 phenotype

Reduced progressive histopathologic changes in the lung;

Reduced inflammatory cytokines

/

[99]

ALI

Injected intraperitoneally with LPS in Sprague-Dawley rats

pMSCs

Reduced the expression of TNF-α and increased IL-10 in RAW264.7 macrophage inflammation model;

Reduced white blood cell count

Alleviated the infiltration of inflammatory cells, pulmonary hyperemia and hemorrhage, and interstitial edema

Downregulated CXCL12

[100]

ALI

Injected intraperitoneally with LPS in Sprague-Dawley rats

BMSC-Exos

Prevented LPS-induced alveolar macrophage apoptosis and autophagy stress

Improved pathological changes in lung tissue;

Improved pulmonary vascular permeability;

Regulated the inflammatory cytokines

Regulated miR-384-5p/Beclin-1 pathway

[101]

ALI

Injected intraperitoneally with LPS in C57BL/6 mice

HS-pretreatedhUCMSCs

Enhanced immunoregulatory effect in inducing M2 macrophage polarization;

Decreased absolute numbers of neutrophils

Improved the pathological changes and lung damage-related indexes; Reduced the proinflammatory cytokine levels

Inhibited NLRP3 inflammasome activation

[102]

ALI

/

BMSCs

Down-regulated the elevated levels of autophagy in macrophages

/

Activated PI3K/Akt/ HO-1 signaling pathway

[39]

ALI

Injected intraperitoneally with LPS in C57BL/6 mice

MSC-Exos

Inhibited LPS-induced glycolysis in macrophages and production of proinflammatory cytokines

Alleviated sepsis-induced ALI and systemic inflammation; Improved survival rate

/

[103]

ALI

Severe burn Sprague-Dawley rats

hUCMSC-Exos

Modulated macrophage M2 polarization

Reduced inflammation and oxidative stress

Regulated miR-451 /MIF/PI3K/AKT signaling pathway

[43]

ALI

Injected intraperitoneally with LPS in C57BL/6 mice

hUCMSCs

Increased PD-L1 expression in the lung macrophages

Decreased total protein exudation concentration and cell number in BALF; Reduced pathological damage and inflammation

Regulated COX2/PGE2 signaling pathway

[36]

ALI

Injected with LPS in C57BL/6 mice

BMSCs

Suppressed the activation of alveolar macrophages

Decreased total protein exudation concentration;

Alleviated alveolar epithelial damage;

Reduced inflammation

Regulated PGE2/EP4R signaling pathway

[104]

ALI

Ligated and punctured cecum in C57BL/6 mice

AMSC-Exos

Inhibited the LPS-mediated release of IL-27 in macrophages;

Reduced the number of pulmonary macrophages

Decreased pulmonary edema and pulmonary vascular leakage;

Reduced inflammation

/

[105]

ALI

Injected with LPS in C57BL/6 mice

AMSC-Exos

Rendered macrophages shifting from M1 proinflammatory to M2-polarized anti-inflammatory phenotype

Alleviated lung inflammation and injury

Transferred mitochondrial component

[46]

ALI

Injected with LPS in C57BL/6 mice

Nrf2 -hAMSC-EVs

Promoted M2-like polarization;

Inhibited infiltration of neutrophils

Reduced apoptosis and inflammation

Inhibited the activation of the NLRP3 inflammasome

[106]

ALI

Injected with LPS in C57BL/6 mice

Hypoxia-preconditioned MSC-CM

Promoted anti-inflammatory polarization; Restored efferocytosis of macrophages

Promoted resolution of inflammation

/

[107]

ALI

Injected with LPS in C57BL/6 mice

MSC-EVs

Promoted M2-like polarization

Reduced the expression of pro-inflammatory cytokines, increased the expression of anti-inflammatory cytokines; Decreased pathological scores

/

[108]

ALI

Ligated and punctured cecum in mice

AMSC-Exos

Promoted M2 polarization and TGF -β secretion

Inhibited inflammatory responses

/

[109]

ALI

Injected with LPS in C57BL/6 mice

PEG2-MSCs

Promoted M2 polarization;

Decreased absolute numbers of neutrophils

Reduced cellular infiltration;

Reduced histopathological changes and pro-inflammatory cytokines and increased anti-inflammatory cytokines

/

[32]

ALI

Injected with LPS in C57BL/6 mice

UCMSC-ABs

Inhibited pro‐inflammatory polarization and cytokines production of macrophages;

Decreased absolute numbers of neutrophils

Suppressed lung inflammation

Regulated PDL1–PD1 pathway;

Reprogrammed metabolic pathways

[110]

ALI

Injected with E.coil in ICR mice

UCMSCs

Regulated on M1/M2 macrophage polarization;

Decreased absolute numbers of neutrophils

Attenuated lung injury and inflammation

Secreted SOCS3

[111]

ALI

Cardiopulmonary bypass related lung injury in Sprague-Dawley rats

BMSC-Exos

Suppressed ROS production and down-regulated the levels of inflammatory cytokines of macrophages

Attenuated histological changes; Down-regulated inflammatory cytokine levels; Alleviated oxidative stress

Regulated NF-κB p65 and Akt/Nrf2/HO-1 signaling pathways

[112]

ALI

/

LPS-BMSC-Exos

Suppressed pro-inflammatory polarization and promoted anti-inflammatory polarization of alveolar macrophages

Suppressed lung inflammation

Regulated miR- 150-3p/ INHBA signaling pathway

[44]

ARDS

Injected intraperitoneally with LPS in C57BL/6 mice

BMSC-Exos

Ameliorated LPS-induced alveolar macrophage M1 polarization

Exerted anti-inflammatory effects

Inhibited glycolysis via inhibition of HIF-1α

[113]

ARDS

Injected with LPS in BALB/c mice

hUCMSCs

Promoted M2-like polarization;

Decreased absolute numbers of neutrophils

Improved lung injury; Attenuated inflammatory cell infiltration

/

[114]

ARDS

Injected with

Klebsiella pneumoniae in C57BL/6 mice

PMSCs

Preserved resident alveolar macrophage over bone marrow–recruited macrophage and drived the overall milieu to an M2 immunomodulatory phenotype;

Enhanced multiple antibacterial functions in alveolar macrophage

Decreased pulmonary inflammation and tissue injury

Secreted IL-1β

[115]

ARDS

/

hUCMSCs

Increased IL-10 expression in alveolar macrophages;

Induced alveolar macrophage polarization

/

Regulated STC1/ PI3K/AKT/mTOR pathway

[37]

Asthma

Injected intraperitoneally with OVA in BALB/c mice

hUCMSCs

Reduced M2 macrophages;

Decreased absolute numbers of eosinophils

Reducted airway hyperresponsiveness and inflammation

/

[52]

Asthma

Instillated intranasally

with total house dust mite extracts in C57BL/6 mice

Serum from asthmatic mice-stimulated BMSCs

Induced further macrophage polarization to M2 profile;

Decreased absolute numbers of neutrophils and eosinophils

Reducted lung inflammation and remodeling;

Improved lung mechanics

/

[53]

Asthma

Injected intraperitoneally with OVA/CFA in BALB/c mice

hUCMSC-Exos

Regulated macrophage polarization;

Decreased absolute numbers of neutrophils

Reduced inflammation

Regulated NF-κB and PI3K/AKT signaling dependent on TRAF1

[116]

Asthma

Injected intraperitoneally with OVA in BALB/c mice

MSC-EVs

Inhibited the recruitment and polarization of lung macrophages;

Decreased absolute numbers of eosinophils

Ameliorated allergic airway inflammation

/

[54]

Asthma

Injected intraperitoneally with OVA in C57BL/6 mice

MSC-Exos

Enhanced lung interstitial macrophages ratios and high level of IL-10;

Decreased absolute numbers of eosinophils

Decrease inflammation index, histological mucus index, total cells and cytokines

/

[55]

Asthma

IL-13 transgenic mice

Liproxstatin-1-primed hUCMSCs/

hUCMSCs

Alterated lung macrophage populations;

Decreased absolute numbers of neutrophils and eosinophils

Reduced airway inflammation and fibrosis

/

[117, 118]

Asthma

Injected intraperitoneally with IL-33 in C57BL/6 mice

iPSC-MSC-EV

Mitigated the activation of ILC2s

Ameliorated ILC2-dominant allergic airway inflammation

Delivered miR-146a-5p

[56]

Asthma

Instillated intranasally

with total house dust mite extracts in BALB/c mice

BMSCs

Decreased absolute numbers of neutrophils, eosinophils and lymphocytes;

Induced lung macrophage polarization into suppressive phenotype

Inhibited airway hyper-responsiveness and bronchoconstriction;

Decreased airway inflammation

/

[119]

Asthma

Instillated intranasally

with total house dust mite extracts in C57BL/6 mice

Eicosapentaenoic acid -stimulated BMSCs

Induced macrophage polarization to the M2;

Decreased absolute numbers of neutrophils and eosinophils

Reduced lung morphological changes, remodeling, and mucus hypersecretion;

Improved lung mechanics

/

[120]

IPF

Injected intratracheal with bleomycin in C57BL/6 mice

hUCMSCs

Reduced M2c subset of M2 monocyte-derived macrophages;

Decreased absolute numbers of neutrophils and eosinophils

Attenuated inflammation and the degree of lung fibrosis

/

[121]

IPF

Injected intratracheal with bleomycin in C57BL/6 mice

hAMSCs

Increased macrophage polarization toward M2, and reduced the antigen-presentation potential of macrophages and dendritic cells

Decreased alveolar obliteration;

Decreased extracellular matrix proteins and α‐SMA

/

[21]

BPD

Hyperoxia-induced in FVB mice/ Sprague-Dawley rats

MSC-Exos

Regulated macrophage phenotype

Restored lung architecture;

Improved pulmonary development and ameliorates septal fibrosis;

Rescued loss of peripheral pulmonary blood vessels and peripheral pulmonary arterial remodeling;

Modulated inflammation

/

[122, 123]

BPD

Hyperoxia-induced in pregnant Sprague-Dawley rats

hUCMSCs

Regulated Macrophage Polarization

Attenuated inflammation

Regulated PTX3/TSG14 pathway

[124]

BPD

Hyperoxia-induced in mice

hUCMSCs

Decreased FPR2 levels in alveolar macrophages

Reduced levels of inflammatory cytokines (IL-1α and TNF-α)

/

[125]

Silicosis

Instilled intratracheally silica suspension in C57BL/6 mice

BMSCs

Decreased the macrophage infiltration

Attenuated inflammation

Regulated the activation of inflammasome by secreting TSG-6

[126]

PAH

Injected with the VEGF receptor 2 antagonist in Sprague-Dawley rats

MSC-EVs

Induced further macrophage polarization to M2 profile

Reduced right ventricular hypertrophy and muscularization of peripheral pulmonary vessel

/

[127]

DAH

Injected intraperitoneally with sterile filtrated pristine in C57BL/6 J mice

hUCMSC-Exos

Enhanced M2 polarization

Alleviated pathological symptoms;

Attenuated the alveolar injuries and inflammatory responses

/

[128]

RILI

Radiated with 20 Gy 60Co γ-ray in Sprague-Dawley rats

miR-21-knockout BMSCs

Controlled macrophage polarization

Decreased RILI-induced acute inflammation;

Reduced mortality in rats with RILI

/

[129]