title: Hypoxia precondition promotes adipose-derived mesenchymal stem cells based repair of diabetic erectile dysfunction via augmenting angiogenesis and neuroprotection.
abstract: 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.
authors: Department of Traditional Chinese Medicine, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China.
authors: XiYou
authors: X
authors: Wang
authors: Department of Urology, PLA Navy General Hospital, No 6 Fucheng Road, Hai dian District, Beijing 100048, People's Republic of China.
authors: CuiLong
authors: C
authors: Liu
authors: Department of Traditional Chinese Medicine, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China.
authors: ShaoDan
authors: S
authors: Li
authors: Department of Urology, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China.
authors: Yong
authors: Y
authors: Xu
authors: Department of Urology, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China.
authors: Ping
authors: P
authors: Chen
authors: Department of Traditional Chinese Medicine, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China.
authors: Yi
authors: Y
authors: Liu
authors: Department of Urology, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China.
authors: Qiang
authors: Q
authors: Ding
authors: Department of Urology, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China.
authors: Wasilijiang
authors: W
authors: Wahafu
authors: Department of Urology, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China.
authors: BaoFa
authors: B
authors: Hong
authors: Department of Traditional Chinese Medicine, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China.
authors: MingHui
authors: M
authors: Yang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D048909:Diabetes Complications / Q000628:therapy*; D007172:Erectile Dysfunction / Q000209:etiology / Q000628:therapy*; D007150:Immunohistochemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D000066829:Neuroprotection / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers