Hypoxia precondition promotes adipose-derived mesenchymal stem cells based repair of diabetic erectile dysfunction via augmenting angiogenesis and neuroprotection.
Hypoxia precondition promotes adipose-derived mesenchymal stem cells based repair of diabetic erectile dysfunction via augmenting angiogenesis and neuroprotection.
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DOI：
10.1371/journal.pone.0118951
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yang M
中科院分区：
文献类型：
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作者：
Wang X;Liu C;Li S;Xu Y;Chen P;Liu Y;Ding Q;Wahafu W;Hong B;Yang M
本研究的目的是研究缺氧预处理是否可以提高脂肪源性间充质干细胞（AMSCs）对糖尿病性勃起功能障碍（DED）的治疗效果。用常氧（20% O2, N-AMSCs）或亚致死缺氧（1% O2, H-AMSCs）预处理AMSCs。低氧暴露上调AMSCs中几种血管生成和神经保护相关细胞因子的表达，包括血管内皮生长因子（VEGF）及其受体FIK-1、血管紧张素（Ang-1）、碱性成纤维细胞生长因子（bFGF）、脑源性神经营养因子（BDNF）、胶质细胞源性神经营养因子（GDNF）、基质源性因子-1 （SDF-1）及其CXC趋化因子受体4 （CXCR4）。采用链脲佐菌素（60 mg/kg）腹腔注射诱导DED大鼠，随机分为3组：生理盐水组：海绵内注射磷酸盐缓冲盐水；N-AMSCs组：注射N-AMSCs；H-AMSCs组：注射H-AMSCs。10只大鼠未作任何处理作为正常对照。注射后4周，测量平均动脉压（MAP）和海绵体内压（ICP）。评估海绵体组织中内皮细胞、平滑肌、背神经的含量。与N-AMSCs和生理盐水相比，海螺内注射H-AMSCs可显著提高ICP和ICP/MAP （p<0.05）。免疫荧光分析显示，MSCs对勃起功能的改善与内皮标志物（CD31和vWF）和平滑肌标志物（α-SMA）的表达增加（p<0.01）显著相关。同时，注射H-AMSCs的大鼠nNOS的表达也明显高于注射N-AMSCs或生理盐水的大鼠。提示MSCs缺氧预处理是提高其治疗DED效果的有效途径，可能与MSCs增强血管生成和神经保护作用有关。
The aim of the present study was to examine whether hypoxia preconditioning could improve therapeutic effects of adipose derived mesenchymal stem cells (AMSCs) for diabetes induced erectile dysfunction (DED). AMSCs were pretreated with normoxia (20% O2, N-AMSCs) or sub-lethal hypoxia (1% O2, H-AMSCs). The hypoxia exposure up-regulated the expression of several angiogenesis and neuroprotection related cytokines in AMSCs, including vascular endothelial growth factor (VEGF) and its receptor FIK-1, angiotensin (Ang-1), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), stromal derived factor-1 (SDF-1) and its CXC chemokine receptor 4 (CXCR4). DED rats were induced via intraperitoneal injection of streptozotocin (60 mg/kg) and were randomly divided into three groups—Saline group: intracavernous injection with phosphate buffer saline; N-AMSCs group: N-AMSCs injection; H-AMSCs group: H-AMSCs injection. Ten rats without any treatment were used as normal control. Four weeks after injection, the mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured. The contents of endothelial, smooth muscle, dorsal nerve in cavernoursal tissue were assessed. Compared with N-AMSCs and saline, intracavernosum injection of H-AMSCs significantly raised ICP and ICP/MAP (p<0.05). Immunofluorescent staining analysis demonstrated that improved erectile function by MSCs was significantly associated with increased expression of endothelial markers (CD31 and vWF) (p<0.01) and smooth muscle markers (α-SMA) (p<0.01). Meanwhile, the expression of nNOS was also significantly higher in rats receiving H-AMSCs injection than those receiving N-AMSCs or saline injection. The results 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.
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影响因子：
23.4
作者：
Fall, Papa Ahmed;Izikki, Mohamed;Yiou, Rene
通讯作者：
Yiou, Rene
DOI：
10.1152/ajpheart.00261.2002
发表时间：
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影响因子：
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