PMID- 25790284 OWN - NLM STAT- MEDLINE DCOM- 20151230 LR - 20220409 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 3 DP - 2015 TI - Hypoxia precondition promotes adipose-derived mesenchymal stem cells based repair of diabetic erectile dysfunction via augmenting angiogenesis and neuroprotection. PG - e0118951 LID - 10.1371/journal.pone.0118951 [doi] LID - e0118951 AB - 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 (alpha-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. FAU - Wang, XiYou AU - Wang X AD - 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. FAU - Liu, CuiLong AU - Liu C AD - Department of Urology, PLA Navy General Hospital, No 6 Fucheng Road, Hai dian District, Beijing 100048, People's Republic of China. FAU - Li, ShaoDan AU - Li S AD - 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. FAU - Xu, Yong AU - Xu Y AD - Department of Urology, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China. FAU - Chen, Ping AU - Chen P AD - Department of Urology, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China. FAU - Liu, Yi AU - Liu Y AD - 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. FAU - Ding, Qiang AU - Ding Q AD - Department of Urology, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China. FAU - Wahafu, Wasilijiang AU - Wahafu W AD - Department of Urology, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China. FAU - Hong, BaoFa AU - Hong B AD - Department of Urology, Chinese People's Liberation Army General Hospital, No 28 Fuxing Road, Hai dian District, Beijing 100853, People's Republic of China. FAU - Yang, MingHui AU - Yang M AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150319 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (DNA Primers) SB - IM MH - Adipose Tissue/*cytology MH - Analysis of Variance MH - Animals MH - Blotting, Western MH - Cell Differentiation/physiology MH - Cell Hypoxia/*physiology MH - DNA Primers/genetics MH - Diabetes Complications/*therapy MH - Erectile Dysfunction/etiology/*therapy MH - Immunohistochemistry MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Neovascularization, Physiologic/*physiology MH - Neuroprotection/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction PMC - PMC4366267 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/03/20 06:00 MHDA- 2015/12/31 06:00 PMCR- 2015/03/19 CRDT- 2015/03/20 06:00 PHST- 2014/02/16 00:00 [received] PHST- 2015/01/20 00:00 [accepted] PHST- 2015/03/20 06:00 [entrez] PHST- 2015/03/20 06:00 [pubmed] PHST- 2015/12/31 06:00 [medline] PHST- 2015/03/19 00:00 [pmc-release] AID - PONE-D-14-07317 [pii] AID - 10.1371/journal.pone.0118951 [doi] PST - epublish SO - PLoS One. 2015 Mar 19;10(3):e0118951. doi: 10.1371/journal.pone.0118951. eCollection 2015.