title: Intramyocardial injection of hypoxia-preconditioned adipose-derived stromal cells treats acute myocardial infarction: an in vivo study in swine.
abstract: Hypoxic preconditioning is a promising method for improving the anti-apoptotic and paracrine signaling capabilities of adipose-derived stromal cells (ADSCs). The purpose of this study was to analyze the influence of different hypoxic conditions on ADSCs and the therapeutic effects of hypoxia-preconditioned ADSCs (HPADSCs) on an animal model of myocardial infarction (MI). For the in vitro studies, ADSCs were divided into five groups and cultured in different oxygen concentrations (1, 3, 5, 10, and 21 %). After 24 h, RT-PCR and western blots showed that 3 % oxygen preconditioning could improve the viability and cytokine secretion of the ADSCs. A Matrigel assay indicated that the HPADSC-conditioned medium could stimulate endothelial cells to form capillary-like tubes. For the in vivo studies, MI was induced by coronary occlusion in 24 mature Chinese minipigs. The animals were divided into three groups and treated by intramyocardial injection with vehicle alone (saline group), with 1 × 10(8) ADSCs cultured in normoxic conditions (ADSCs group) or with 1 × 10(8) ADSCs precultured in 3 % oxygen (HPADSCs group). SPECT and echocardiography demonstrated that cardiac function was improved significantly in the HPADSC transplant group compared with the vehicle control group (P < 0.05). Immunofluorescence showed fewer apoptotic cells and more small- to medium-sized vessels in the HPADSC transplantation group (P < 0.05). Three percent oxygen is the optimum preconditioning treatment for ADSCs. HPADSC transplantation can prevent ventricular remodeling and reduce the infarct size.
authors.affiliation: Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital Cardiovascular Clinical Hospital of Tianjin Medical University, 61# Third Avenue Tianjin Economic Development Area, Tianjin, 300457, China.
authors.forename: Yiyao
authors.initials: Y
authors.lastname: Jiang
authors.forename: Pengyu
authors.initials: P
authors.lastname: Chang
authors.forename: Yu
authors.initials: Y
authors.lastname: Pei
authors.forename: Baojiang
authors.initials: B
authors.lastname: Li
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Delin
authors.initials: D
authors.lastname: Zhu
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006334:Heart Function Tests; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D007267:Injections; D019157:Ischemic Preconditioning, Myocardial; D019394:Ki-67 Antigen / Q000378:metabolism; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D013552:Swine; D013556:Swine, Miniature; D015899:Tomography, Emission-Computed, Single-Photon; D014463:Ultrasonography; D055815:Young Adult; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D001613:beta 2-Microglobulin