Correction of Diabetic Erectile Dysfunction with Adipose Derived Stem Cells Modified with the Vascular Endothelial Growth Factor Gene in a Rodent Diabetic Model
Guihua Liu,Guihua Liu,Xiangzhou Sun,Jun Bian,Rongpei Wu,Rongpei Wu,Xuan Guan,Bin Ouyang,Yan-Ping Huang,Haipeng Xiao,Dao-Sheng Luo,Anthony Atala,Yuanyuan Zhang,Chunhua Deng +13 more
TLDR
Western blot and immunofluorescent analysis demonstrated that improved erectile function by ADSCs-VEGF was associated with increased expression of endothelial markers, smooth muscle markers, and pericyte markers in cavernoursal tissue.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.read more
Citations
More filters
Journal ArticleDOI
Human Urine-Derived Stem Cells Alone or Genetically-Modified with FGF2 Improve Type 2 Diabetic Erectile Dysfunction in a Rat Model
Bin Ouyang,Xiangzhou Sun,Da-Yu Han,Shenfu Chen,Bing Yao,Yong Gao,Jun Bian,Yan-Ping Huang,Ya-Dong Zhang,Zi Wan,Bin Yang,Haipeng Xiao,Zhou Songyang,Guihua Liu,Yuanyuan Zhang,Chunhua Deng +15 more
TL;DR: The paracrine effect of USCs or USCs-FGF2 induced improvement of erectile function in type 2 diabetic rats by recruiting resident cells and increasing the endothelial expression and contents of smooth muscle.
Journal ArticleDOI
Hypoxia precondition promotes adipose-derived mesenchymal stem cells based repair of diabetic erectile dysfunction via augmenting angiogenesis and neuroprotection.
Xiyou Wang,Liu Cuilong,Shao-dan Li,Yong Xu,Ping Chen,Yi Liu,Qiang Ding,Wasilijiang Wahafu,Baofa Hong,Minghui Yang +9 more
TL;DR: It is suggested that hypoxic preconditioning of MSCs was an effective approach to enhance their therapeutic effect for DED, which may be due to their augmented angiogenesis and neuroprotection.
Journal ArticleDOI
A genome-wide association study to identify candidate genes for erectile dysfunction.
Elham Kazemi,Javaad Zargooshi,Marzieh Kaboudi,Parviz Heidari,Danial Kahrizi,Behzad Mahaki,Youkhabeh Mohammadian,Habibolah Khazaei,Kawsar Ahmed +8 more
TL;DR: This study introduced new genes associated with ED, which can be good candidates for further analyzing related to human ED, as well as identified the common cis-regulatory elements of these genes.
Journal ArticleDOI
Stem cell treatment of erectile dysfunction.
TL;DR: A summary of the scientific principles behind SCs and their use for treatment of ED is presented and the different types of SCs used in ED, the methods of delivery tested, and the methods attempted to enhance SC therapy effect are discussed.
Journal ArticleDOI
Transplantation of Human Urine-Derived Stem Cells Transfected With Pigment Epithelium-Derived Factor to Protect Erectile Function in a Rat Model of Cavernous Nerve Injury.
Qiyun Yang,Xin Chen,Tao Zheng,Da-Yu Han,Heng Zhang,Yanan Shi,Jun Bian,Xiangzhou Sun,Kai Xia,Xiaoyan Liang,Guihua Liu,Yuanyuan Zhang,Chunhua Deng +12 more
TL;DR: The paracrine effect of USCs and USCsGFP/PEDF+ prevented the destruction of erectile function and the cavernous structure in the CNIED rat model by nerve protection, thereby improving endothelial cell function, increasing the smooth muscle content, and decreasing fibrosis and cell apoptosis in the cavernously tissue.
References
More filters
Journal ArticleDOI
Endothelial/Pericyte Interactions
TL;DR: This review focuses on the advancement in recent years of the understanding of intercellular communication between endothelial and mural cells with a focus on transforming growth factor α, angiopoietins, platelet-derived growth factor, spingosine-1-phosphate, and Notch ligands and their respective receptors.
Journal ArticleDOI
The role of pericytes in blood-vessel formation and maintenance
Gabriele Bergers,Steven Song +1 more
TL;DR: This review article describes the current knowledge about the nature of pericytes and their functions during vessel growth, vessel maintenance, and pathological angiogenesis.
Journal ArticleDOI
Molecular Understanding of Hyperglycemia's Adverse Effects for Diabetic Complications
Matthew J. Sheetz,George L. King +1 more
TL;DR: Several predominant well-researched theories have been proposed to explain how hyperglycemia can produce the neural and vascular derangements that are hallmarks of diabetes and the potential therapeutic interventions that may prevent diabetic complications in the presence of hyperglyCEmia are summarized.
Journal ArticleDOI
Safety of Cell Therapy with Mesenchymal Stromal Cells (SafeCell): A Systematic Review and Meta-Analysis of Clinical Trials
Manoj M. Lalu,Lauralyn McIntyre,Lauralyn McIntyre,Christina Pugliese,Dean Fergusson,Brent W. Winston,John C. Marshall,John Granton,Duncan J. Stewart,Duncan J. Stewart +9 more
TL;DR: Based on the current clinical trials, MSC therapy appears safe, however, further larger scale controlled clinical trials with rigorous reporting of adverse events are required to further define the safety profile of MSCs.
Journal ArticleDOI
Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing.
TL;DR: The current body of evidence identifying endothelial dysfunction and impaired angiogenesis during diabetes is discussed, with a focus on type 2 diabetes mellitus.