title: Correction of diabetic erectile dysfunction with adipose derived stem cells modified with the vascular endothelial growth factor gene in a rodent diabetic model.
abstract: The aim of this study was to determine whether adipose derived stem cells (ADSCs) expressing vascular endothelial growth factor (VEGF) gene can improve endothelial function, recover the impaired VEGF signaling pathway and enhance smooth muscle contents in a rat diabetic erectile dysfunction (DED) model. DED rats were induced via intraperitoneal injection of streptozotocin (40 mg/kg), and then screened by apomorphine (100 µg/kg). Five groups were used (n = 12/group)-Group 1 (G1): intracavernous injection of lentivirus-VEGF; G2: ADSCs injection; G3: VEGF-expressing ADSCs injection; G4: Phosphate buffered saline injection; G1-G4 were DED rats; G5: normal rats. The mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured at days 7 and 28 after the injections. The components of the VEGF system, endothelial, smooth muscle, pericytes markers in cavernoursal tissue were assessed. On day 28 after injection, the group with intracavernosum injection of ADSCs expressing VEGF displayed more efficiently and significantly raised ICP and ICP/MAP (p<0.01) than those with ADSCs or lentivirus-VEGF injection. Western blot and immunofluorescent analysis demonstrated that improved erectile function by ADSCs-VEGF was associated with increased expression of endothelial markers (VEGF, VEGF R1, VEGF R2, eNOS, CD31 and vWF), smooth muscle markers (a-actin and smoothelin), and pericyte markers (CD146 and NG2). ADSCs expressing VEGF produced a therapeutic effect and restored erectile function in diabetic rats by enhancing VEGF-stimulated endothelial function and increasing the contents of smooth muscle and pericytes.
authors.affiliation: Department of Urology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China ; Wake Forest Institute of Regenerative Medicine, Wake Forest University, Winston Salem, North Carolina, United States of America.
authors.forename: Guihua
authors.initials: G
authors.lastname: Liu
authors.forename: Xiangzhou
authors.initials: X
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Bian
authors.forename: Rongpei
authors.initials: R
authors.lastname: Wu
authors.forename: Xuan
authors.initials: X
authors.lastname: Guan
authors.forename: Bin
authors.initials: B
authors.lastname: Ouyang
authors.forename: Yanping
authors.initials: Y
authors.lastname: Huang
authors.forename: Haipeng
authors.initials: H
authors.lastname: Xiao
authors.forename: Daosheng
authors.initials: D
authors.lastname: Luo
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Deng
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D007172:Erectile Dysfunction / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013311:Streptozocin; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin; D052250:Nitric Oxide Synthase Type III; D040262:Receptors, Vascular Endothelial Growth Factor
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