Sildenafil and cardioprotection. Curr Pharm Des. 2013;19(39):6842-7 Authors: Kukreja RC Abstract PMID: 23590161 [PubMed - indexed for MEDLINE] Therapeutic Potential of Adipose-Derived Stem Cells-Based Micro-Tissues in a Rat Model of Postprostatectomy Erectile Dysfunction. J Sex Med. 2014 Jul 15; Authors: Xu Y, Guan R, Lei H, Li H, Wang L, Gao Z, Song W, Xin Z Abstract PMID: 25042722 [PubMed - as supplied by publisher] Neurotrophic effect of bone marrow mesenchymal stem cells for erectile dysfunction in diabetic rats. Int J Androl. 2012 Aug;35(4):601-7 Authors: Sun C, Lin H, Yu W, Li X, Chen Y, Qiu X, Wang R, Dai Y Abstract PMID: 22428616 [PubMed - indexed for MEDLINE]
pubmed: erectile dysfunction...
NCBI: db=pubmed; Term=Erectile dysfunction and Stem Cell Therapy
The phosphodiesterese-5 (PDE5) inhibitors, including sildenafil (Viagra™), vardenafil (Levitra™), tadalafil (Cialis™) and avanafil (Stendra™) have been developed for the treatment of erectile dysfunction. Moreover, sildenafil and tadalafil have been approved for the management of pulmonary arterial hypertension. A number of preclinical studies have shown that PDE5 inhibitors have powerful protective effect against several clinical scenarios including myocardial ischemia/reperfusion injury, doxorubicin and post-MI, heart failure, cardiac hypertrophy, heart transplantation, Duchenne muscular dystrophy and preconditioning of stem cells. Based on these studies, it appears that sildenafil and other PDE5 inhibitors hold promise for further development as novel drug therapies in cardioprotection.
pubmed: erectile dysfunction...
NCBI: db=pubmed; Term=Erectile dysfunction and Stem Cell Treatment
INTRODUCTION: Stem cells (SCs) show significant benefits in the treatment of postprostatectomy erectile dysfunction (ED). However, the low retention rate of the traditional single-cell strategy at the injection sites limits its therapeutic potential.
AIM: This study aims to investigate the feasibility and mechanism of adipose-derived stem cells (ADSCs)-based micro-tissues (MTs) in the treatment of ED in a rat model of bilateral cavernous nerves (CNs) injury.
METHODS: ADSCs labeled with 5-ethynyl-2-deoxyuridine (EdU) were used to generate MTs with hanging drop method. 10 Sprague-Dawley (SD) rats underwent sham surgery and intracavernous (IC) injection of phosphate buffer solution (PBS) (the sham group). Another 70 rats underwent bilateral CN crush and were then treated with PBS (n = 10, the crush group), dissociated ADSCs (n = 30, the ADSCs group), and MTs (n = 30, the MTs group), respectively. At day 1, 3, 7, 14 (n = 5), and 28 (n = 10) postsurgery, specimens were harvested for histology. At day 28, 10 rats in each group were examined for erectile function before tissue harvest.
MAIN OUTCOME MEASURES: Light microscopy of the dynamic aggregation of the MT, immunohistologic examination of the MTs, the retention and distribution of EdU + ADSCs in the corpus cavernosum (CC), and the penis histological analyses of collagen content, Western blot of functional proteins in MTs, intracavernous pressure recording on CN electrostimulation.
RESULTS: Three-day-old MTs became stable and expressed nerve growth factor, vascular endothelial growth factor, C-X-C chemokine receptor type 4, Wnt5a, and collagen IV. More EdU + ADSCs retained in the CC in the MTs group than that in the ADSCs group. IC injection of MTs resulted in significant restoration of the erectile function and histopathological changes compared with the ADSCs group.
CONCLUSION: IC-injected MTs resulted in a better restoration of erectile function than traditional single-cell strategy. The underlying mechanisms of recovery appear to involve enhanced cellular retention in the penis and upregulation of some paracrine factors. Xu Y, Guan R, Lei H, Li H, Wang L, Gao Z, Song W, and Xin Z. Therapeutic potential of adipose-derived stem cells-based micro-tissues in a rat model of postprostatectomy erectile dysfunction. J Sex Med **;**:**-**.
It has been demonstrated that intracavernous injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) had beneficial effects on improving erectile function in type-1 diabetic rats. This study was designed to investigate the neurotrophic effect of BM-MSCs for type-1 diabetic rats. Streptozocin-induced type-1 diabetic rats were randomly divided into three groups: diabetic group, BM-MSCs-treated group and BM-MSCs-conditioned medium-treated group. At the 3d, 1 and 2w time points after BM-MSCs injection, three randomly selected rats in MSCs group were sacrificed and penile samples were harvested to detect BM-MSCs in penile tissue. Four weeks after intracavernous injection of BM-MSCs or BM-MSCs-conditioned medium, intracavernous pressure (ICP) was assessed to evaluate the erectile function. Immunohistochemistry was used to track labelled BM-MSCs in penile tissue and to detect neuronal nitric oxide synthase (nNOS) and neurofilament (NF) positive fibres in penile dorsal nerve. Enzyme lined immunosorbent assay (ELISA) was used to measure the concentrations of vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in BM-MSCs-conditioned medium. BM- MSCs secreted detectable levels of VEGF, BDNF and NGF. Intracavernous injection of BM-MSCs improved erectile function in diabetic rats. The functional improvement was accompanied by promoted nNOS and NF positive nerve fibres within penile dorsal nerve in type-1 diabetic rats. Histological data revealed a time-dependent decrease in the number of BM-MSCs in the corpus cavernosum following injection. Furthermore, the beneficial effect of BM-MSCs was partially repeated by BM-MSCs-conditioned medium. Intracavernous injection of BM-MSCs is effective in improving nerve regeneration in diabetic rats. Paracrine effects of BM-MSCs are probably involved in the improvement.
Sildenafil and cardioprotection.
Curr Pharm Des. 2013;19(39):6842-7
Authors: Kukreja RC
PMID: 23590161 [PubMed - indexed for MEDLINE]
Therapeutic Potential of Adipose-Derived Stem Cells-Based Micro-Tissues in a Rat Model of Postprostatectomy Erectile Dysfunction.
J Sex Med. 2014 Jul 15;
Authors: Xu Y, Guan R, Lei H, Li H, Wang L, Gao Z, Song W, Xin Z
PMID: 25042722 [PubMed - as supplied by publisher]
Neurotrophic effect of bone marrow mesenchymal stem cells for erectile dysfunction in diabetic rats.
Int J Androl. 2012 Aug;35(4):601-7
Authors: Sun C, Lin H, Yu W, Li X, Chen Y, Qiu X, Wang R, Dai Y
PMID: 22428616 [PubMed - indexed for MEDLINE]