Current status and prospects of basic research and clinical application of mesenchymal stem cells in acute respiratory distress syndrome

Table 1 Recent studies on the mechanism of mesenchymal stem cell action in acute respiratory distress syndrome

Ref.	Time	Animal/cell line	Interference	Pathway	Conclusion/main effect
Zhang et al[112]	2022	C-mice	Human dermal fibroblasts or MSCs were intravenously	CAP	MSC treatment significantly protects mice against bacterial pneumonia or LPS-induced lung injury via the CAP pathway. When the CAP was inhibited through vagotomy (VGX) and pharmacological and genetic ablation experiments, the anti-inflammatory effects of MSCs were markedly reduced in lung injury models
Kakabadze et al[113]	2022	Wistar rats	HPMSCs	-	HPMSCs have the ability to migrate and attach to damaged lung tissue, contributing to the resolution of pathology, restoration of function, and tissue repair in the alveolar space
Wang et al[114]	2022	C-mice	Human placental MSCs	Macrophage polarization pathway	Human PMSC treatment preferentially rescued resident M2 AMΦs over recruited M1 BMMΦs with overall M2 polarization to improve KP-related ARDS survival
Wang et al[115]	2022	SD rats	LRMSC/HMSC-C/HMSC-BM	-	Three kinds of LRMSC, HMSC-C and HMSC-BM are protective against LPS-induced lung injury, HMSC-C was more effective than LRMSC and HMSC-BM to treat LPS-induced lung injury
Zhang et al[116]	2022	C-mice	MSC derived microvesicles	KEGG pathway and GO function	MSV microvesicles treatment was involved in alleviated lung injury and promoting lung tissue repair by dysregulated miRNAs
Xu et al[60]	2022	BALB/c mice	Umbilical cord-derived MSCs	-	Transplantation of UC-MSCs transfected with SP-B could potentiate M2 macrophage polarization and further relieve LPS-stimulated lung injury
Xue et al[117]	2022	C-mice	Bone marrow-derived MSC	-	TGF-β1 from MSCs restored skewed Treg/Th17 levels induced by hypoxic- and LPS-stimulated conditions and reduced inflammation
He et al[118]	2022	Hnsclc cell line A549 (ATCC, CCL-185)	MSCs	CXCL12/CXCR4 signal axis	In vivo transplantation of MSCs significantly attenuated lung injury in ARDS, inhibited serum pro-inflammatory factors in mice, and down-regulated expression of apoptotic and focal factors in lung tissues
Zhang et al[119]	2022	C-mice	Mouse bone marrow-derived MSCs	Wnt/β-catenin transition signaling	MVs released from MSCs exerted protective effects on early fibrosis by suppressing EMT in LPS-induced ARDS
Meng et al[120]	2021	-	MSCs derived from normal mouse bone marrow	Akt/Mtor signaling	MTORC2 like mTORC1 as an important signaling of regulation of MSC-secreted HGF protective against LPS-induced lung endothelial dysfunction
Ishii et al[121]	2021	Adult male Fischer 344 rats	Adipose-derived MSCs	-	AD-MSCs enhanced the barrier function between lung epithelial cells, suggesting that both direct adhesion and indirect paracrine effects strengthened the barrier function of lung alveolar epithelium in vitro
Wang et al[122]	2021	C-mice	Bone MSCs	Vimentin-Rab7a pathway	MSCs can reach the damaged lung tissue through migration, reduce inflammatory responses and alleviate lung injury
Liu et al[123]	2021	SD rats	Bone marrow mesenchymal stem cell	Beclin-1	BMSC-derived exosomes were taken up by the alveolar macrophages and attenuated LPS-induced alveolar macrophage viability loss and apoptosis. Exosomes effectively improved the survival rate of ALI rats, which was associated with alleviating lung pathological changes pulmonary vascular permeability and attenuating inflammatory response

C-mice: C57BL/6 mice; CAP: Cholinergic anti-inflammatory pathway; HPMSCs: Human placental mesenchymal stem cells; PMSCs: Placental MSCs; AMΦs: Alveolar macrophage; BMMΦ: Bone marrow–recruited macrophage; Hnsclc: Human non-small cell lung cancer; KP: Klebsiella pneumonia; LRMSC: Lung resident MSC; HMSC-C: Human chorion-derived MSC; HMSC-BM: Human bone marrow derived MSC; KEGG: Kyoto encyclopedia of genes and genomes; GO: Gene ontology; SP-B: Surfactant protein B; AD-MSC: Adipose tissue-derived MSC; EMT: Epithelial–mesenchymal transition; SD: Sprague-Dawley; mTOR: Mammalian TOR; ARDS: Acute respiratory distress syndrome; ALI: Acute lung injury; TGF-β1: Tumor growth factor-β1.