title: The functional study of human umbilical cord mesenchymal stem cells harbouring angiotensin-converting enzyme 2 in rat acute lung ischemia-reperfusion injury model.
abstract: Acute lung ischemia-reperfusion injury (ALIRI) is featured as non-specific alveolar damage, lung edema and hypoxemia, often occurring within 72 h after surgery. It is the leading cause for primary graft failure and mortality after lung surgery and transplantation. Here we aimed to find a more effective therapeutic approach to treat ALIRI. We evaluated the combinational effects of human umbilical cord mesenchymal stem cells (HUMSCs) and angiotensin-converting enzyme 2 (ACE2) in the rat ALIRI model. HUMSCs were isolated for lentiviral-ACE2 transfection. Fifty rats were randomly divided into five groups: sham surgery, physiological saline (PS), ACE2, HUMSCs and HUMSCs-ACE2 group. Several physiological, biochemical and histological indicators were examined and compared among the five groups, such as blood oxygen saturation (Sat O2 %) and right ventricular systolic blood pressure (RVSBP), pulmonary morphology observations, several kinds of cell markers and the abundance of glutathione reductase (GR), glutathione peroxidase (GPX) and NAD(P)H quinone oxidoreductase (NQO1). Compared with HUMSCs and ACE2 groups, HUMSCs-ACE2 group showed lighter lung injuries, higher CD31 and vWF expression (endothelial cell surface markers), lower γ-H2AX (DNA damage marker) and CD68 (inflammatory cell marker) and higher anti-oxidants expression (GR, GPX and NQO1). The results indicated that HUMSCs harbouring ACE2 were more effective than either HUMSCs or ACE2 alone in alleviating the ALIRI damages. The synergistic effects of HUMSCs and ACE2 provide informative clues for mechanism study and therapeutic method development of ALIRI.
authors.affiliation: Department of Thoracic Surgery, First People's Hospital, Affiliated to Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Fabing
authors.initials: F
authors.lastname: Liu
authors.forename: Fengying
authors.initials: F
authors.lastname: Gao
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D000085962:Angiotensin-Converting Enzyme 2; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D006657:Histones; D010088:Oxidoreductases; D007703:Peptidyl-Dipeptidase A; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C468783:H2AX protein, human; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat
keywords: acute lung ischemia-reperfusion injury; angiotensin-converting enzyme 2; human umbilical cord mesenchymal stem cells; lung edema