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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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Hypoxia preconditioning upregulates angiogenesis-related factors in AMSCs.RT-PCR demonstrated that several cytokines that were related to neovascularization or vascular protection were significantly unregulated in hypixia-preconditioned AMSCs compared with normoxia ones (P<0.01 in each factor).
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pone.0118951.g002: Hypoxia preconditioning upregulates angiogenesis-related factors in AMSCs.RT-PCR demonstrated that several cytokines that were related to neovascularization or vascular protection were significantly unregulated in hypixia-preconditioned AMSCs compared with normoxia ones (P<0.01 in each factor).

Mentions: It has been reported that the living environment of MSCs in vivo is maintained at a low oxygen condition of ~4% [32]. We thus selected the hypoxia treatment of 1% O2. As referred to the normoxia in this report, the atmospheric oxygen level of 20% is adopted. Based on previous studies [16,17], it have been confirmed that hypoxia could induce the secretion of cytokines involving in promotion of angiogenesis. We hypothesized that hypoxic incubation could up-regulate the angiogenesis related cytokines. In the study, we found that 24 h exposures of AMSCs to normoxia (20% O2) or hypoxia (1%O2) did not trigger significant cell death as tested with trypan blue staining (data not shown). RT-PCR analysis showed that AMSCs with normoxia treatment (N-AMSCs) expressed a detectable level of several angiogenic cytokines, including bFGF, VEGF, VEGF receptor Flk-1 and Ang-1 (Fig. 2). Compared with N-AMSCs, the expression of the above angiogenic cytokines was up-regulated in hypoxia preconditioned AMSCs (Fig. 2).


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)

Hypoxia preconditioning upregulates angiogenesis-related factors in AMSCs.RT-PCR demonstrated that several cytokines that were related to neovascularization or vascular protection were significantly unregulated in hypixia-preconditioned AMSCs compared with normoxia ones (P<0.01 in each factor).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0118951.g002: Hypoxia preconditioning upregulates angiogenesis-related factors in AMSCs.RT-PCR demonstrated that several cytokines that were related to neovascularization or vascular protection were significantly unregulated in hypixia-preconditioned AMSCs compared with normoxia ones (P<0.01 in each factor).
Mentions: It has been reported that the living environment of MSCs in vivo is maintained at a low oxygen condition of ~4% [32]. We thus selected the hypoxia treatment of 1% O2. As referred to the normoxia in this report, the atmospheric oxygen level of 20% is adopted. Based on previous studies [16,17], it have been confirmed that hypoxia could induce the secretion of cytokines involving in promotion of angiogenesis. We hypothesized that hypoxic incubation could up-regulate the angiogenesis related cytokines. In the study, we found that 24 h exposures of AMSCs to normoxia (20% O2) or hypoxia (1%O2) did not trigger significant cell death as tested with trypan blue staining (data not shown). RT-PCR analysis showed that AMSCs with normoxia treatment (N-AMSCs) expressed a detectable level of several angiogenic cytokines, including bFGF, VEGF, VEGF receptor Flk-1 and Ang-1 (Fig. 2). Compared with N-AMSCs, the expression of the above angiogenic cytokines was up-regulated in hypoxia preconditioned AMSCs (Fig. 2).

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