title: Combination therapy with human umbilical cord mesenchymal stem cells and angiotensin-converting enzyme 2 is superior for the treatment of acute lung ischemia-reperfusion injury in rats.
abstract: Acute lung ischemia-reperfusion injury (ALIRI) is a serious disease that seriously affects human's life. In this study, we aimed to explore a more effective treatment method by combining human umbilical cord mesenchymal stem cells (HUMSCs) and angiotensin-converting enzyme 2 (ACE2) for ALIRI. Fifty rats were firstly divided into five groups, namely sham surgery group (sham) and four model groups (model, ACE2, HUMSCs and HUMSCs + ACE2) that were reperfused with 0.1 ml physiological saline (PS), 0.1 ml PS containing 1 × 10(6) lentiviral-ACE2/HUMSCs/ACE2 + UMSCs, respectively. Quantitative reverse transcription-PCR (qRT-PCR) and western blot assays were then conducted to detect the messenger RNA (mRNA) and protein levels of inflammatory cytokines [intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), tumour necrosis factor α (TNF-α), nuclear factor κB (NF-κB), platelet-derived growth factor (PDGF) and angiotensin II (Ang II)], antioxidant proteins [NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1)], DNA damage and apoptotic indicators [BCL2-associated X (Bax), cleaved caspase-3 (C-Csp 3), cleaved-poly(ADP-ribose) polymerase (C-PARP), Y-H2AX], anti-apoptotic indicator (Bcl-2) and smooth muscle cell proliferation indicator [connexin 43 (Cx43)]. According to the qRT-PCR and western results, the mRNA and protein expression levels of ICAM-1, VCAM-1, TNF-α, NF-κB, PDGF, Bax, C-Csp 3, C-PARP and Y-H2AX were significantly higher in model group than those in sham group and they were significantly reduced by HUMSCs or ACE2 treatment (P < 0.05). On the contrary, Bcl-2 showed an opposite expression trend with the previous proteins. The mRNA and protein levels of NQO1 and HO-1 were sequentially increased in sham, model, ACE2, HUMSCs and HUMSCs + ACE2 groups. Besides, HUMSCs combined with ACE2 exhibited a better inhibition effect on ALIRI than HUMSCs or ACE2 alone (P < 0.05). In summary, HUMSCs combined with ACE2 was demonstrated to have the best therapeutic effect on ALIRI through anti-inflammation, oxidative stress and anti-apoptotic processes.
authors.affiliation: Department of Thoracic Surgery, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaomiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Fengying
authors.initials: F
authors.lastname: Gao
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Yan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ruan
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy*; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2
keywords: acute lung ischemia-reperfusion injury; angiotensin-converting enzyme; apoptosis; human umbilical cord mesenchymal stem cells; inflammation; oxidative stress