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Hypoxia precondition promotes adipose-derived mesenchymal stem cells based repair of diabetic erectile dysfunction via augmenting angiogenesis and neuroprotection.

Wang X, Liu C, Li S, Xu Y, Chen P, Liu Y, Ding Q, Wahafu W, Hong B, Yang M - PLoS ONE (2015)

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

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Related in: MedlinePlus

Body weight, blood glucose and erectile function.STZ injection caused a significant body weight loss at the 4st week and continual increase of blood glucose concentration in the diabetic groups compared to age-matched controls. There were no difference among diabetes groups in both body weights and blood glucose level. Erectile function: The ICP value of treatment with N-AMSCs or H-AMSCs is increased and the ratio of total ICP to MAP was also calculated. *P<0.05;
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pone.0118951.g005: Body weight, blood glucose and erectile function.STZ injection caused a significant body weight loss at the 4st week and continual increase of blood glucose concentration in the diabetic groups compared to age-matched controls. There were no difference among diabetes groups in both body weights and blood glucose level. Erectile function: The ICP value of treatment with N-AMSCs or H-AMSCs is increased and the ratio of total ICP to MAP was also calculated. *P<0.05;

Mentions: Compared with age-matched nondiabetic controls, a significant decrease of body weights in the diabetic rats was observed 4 weeks after STZ injection (Fig. 5) (p<0.05). The injection also triggered a significant increase of blood glucose levels at the beginning, the 1st week and the 4th weak (p<0.05). After 4 weeks, both blood glucose concentration and body weights demonstrated no significant difference between MSC treated rats and untreated ones. Measurement of mean arterial pressure (MAP) showed that no significant difference existed between the four groups, indicating that diabetic induction did not affect the MAP of rats.


Hypoxia precondition promotes adipose-derived mesenchymal stem cells based repair of diabetic erectile dysfunction via augmenting angiogenesis and neuroprotection.

Wang X, Liu C, Li S, Xu Y, Chen P, Liu Y, Ding Q, Wahafu W, Hong B, Yang M - PLoS ONE (2015)

Body weight, blood glucose and erectile function.STZ injection caused a significant body weight loss at the 4st week and continual increase of blood glucose concentration in the diabetic groups compared to age-matched controls. There were no difference among diabetes groups in both body weights and blood glucose level. Erectile function: The ICP value of treatment with N-AMSCs or H-AMSCs is increased and the ratio of total ICP to MAP was also calculated. *P<0.05;
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4366267&req=5

pone.0118951.g005: Body weight, blood glucose and erectile function.STZ injection caused a significant body weight loss at the 4st week and continual increase of blood glucose concentration in the diabetic groups compared to age-matched controls. There were no difference among diabetes groups in both body weights and blood glucose level. Erectile function: The ICP value of treatment with N-AMSCs or H-AMSCs is increased and the ratio of total ICP to MAP was also calculated. *P<0.05;
Mentions: Compared with age-matched nondiabetic controls, a significant decrease of body weights in the diabetic rats was observed 4 weeks after STZ injection (Fig. 5) (p<0.05). The injection also triggered a significant increase of blood glucose levels at the beginning, the 1st week and the 4th weak (p<0.05). After 4 weeks, both blood glucose concentration and body weights demonstrated no significant difference between MSC treated rats and untreated ones. Measurement of mean arterial pressure (MAP) showed that no significant difference existed between the four groups, indicating that diabetic induction did not affect the MAP of rats.

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

Show MeSH
Related in: MedlinePlus