Current Perspectives on Stem Cell Therapy for Erectile Dysfunction

Peak, Taylor C.; Anaissie, James

doi:10.1016/j.sxmr.2016.02.003

Cited by 29 publications

(23 citation statements)

References 73 publications

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“…37 However, MSC implantation in the MPG promoted nerve regeneration, while MSC implantation in the corpus cavernosum prevented degeneration of SM. 38 The leading cause of fibrosis in the corpus cavernosum after BCNI is neuronal Wallerian degeneration in the MPG and the CN. 39 Transplantation of MSCs around the MPG may result in secretion of neurotrophic factors to promote nerve regeneration at the CNI site.…”

Section: Discussionmentioning

confidence: 99%

Co‐overexpression of VEGF and GDNF in adipose‐derived stem cells optimizes therapeutic effect in neurogenic erectile dysfunction model

Yang

Ouyang

et al. 2020

Cell Proliferation

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Objectives To evaluate the rapid repair potential of adipose‐derived stem cells (ADSCs) co‐overexpressing VEGF and GDNF on bilateral cavernous nerve injury (BCNI) in rat models. Progressive fibrosis of the penis that occurs shortly after BCNI is a key cause of clinical treatment difficulty of erectile dysfunction (ED). Traditional medications are ineffective for ED caused by BCNI. ADSCs have shown therapeutic effects in animal models, but disappointing in clinical treatment suggests that we should explore optimal treatment of it. Materials and methods We extracted ADSCs from rat epididymis. Lentiviral transfection was verified by western blot and immunofluorescence. Thirty‐six SD rats (10 weeks old) were randomly divided into six groups (n = 6 per group): sham surgery, and remaining five BCNI groups transplanted PBS or ADSCs which were genetically modified by vehicle, VEGF (ADSC‐V), GDNF (ADSC‐G), or VEGF&GDNF (ADSC‐G&V) around major pelvic ganglion (MPG). We investigated the therapeutic effects of BCNI rat model which is characterized by ED, penile tissue fibrosis and hypoxia, and lack of nitrogen nerves or vascular atrophy. Results Erectile function was almost recovered after 2 weeks of transplantation of ADSC‐G&V, promoted cavernous nerve repair, prevented penile fibrosis and preserving the vascular endothelium, which was significant differences amongst ADSC‐V or ADSC‐G. Moreover, GM‐ADSCs were detected in MPG and penis, indicating that their participation in repair of target organs and transverse nerves. Conclusions These promising data indicate that ADSCs co‐overexpressed VEGF and GDNF‐induced synergistic effects, make it a potential tool for recovering of erectile function speedily after BCNI.

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Section: Discussionmentioning

confidence: 99%

Co‐overexpression of VEGF and GDNF in adipose‐derived stem cells optimizes therapeutic effect in neurogenic erectile dysfunction model

Yang

Ouyang

et al. 2020

Cell Proliferation

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“…Increased living standards have been accompanied by an increased demand for erectile dysfunction (ED) therapy, especially in elderly men who suffer from diabetes mellitus (DM) [1,2]. The main current treatment strategy for ED is phosphodiesterase 5 inhibitor (PDE5I), which affects angiectasis of the corpus cavernosum [3]. However, for ED caused by DM, PDE5I is not sufficiently effective [4,5].…”

Section: Introductionmentioning

confidence: 99%

Engineered Mesenchymal Stem Cells Expressing Stromal Cell-derived Factor-1 Improve Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats

Jeon

Zhu

Bae

et al. 2018

IJMS

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Effective therapies for erectile dysfunction (ED) associated with diabetes mellitus (DM) are needed. In this study, the effects of stromal cell-derived factor-1 (SDF-1)-expressing engineered mesenchymal stem cells (SDF-1 eMSCs) and the relevant mechanisms in the corpus cavernosum of a streptozotocin (STZ)-induced DM ED rat model were evaluated. In a randomized controlled trial, Sprague–Dawley (SD) rats (n = 48) were divided into four groups (n = 12/group): Normal (control), DM ED (diabetes induced by STZ), DM ED + BM-MSC (treated with bone marrow [BM]-derived MSCs), and DM ED + SDF-1 eMSC (treated with SDF-1-expressing BM-MSCs). After four weeks, intracavernosal pressure (ICP), an indicator of erectile function, was 0.75 ± 0.07 in the normal group, 0.27 ± 0.08 in the DM ED group, 0.42 ± 0.11 in the DM ED + BM-MSC group, and 0.58 ± 0.11 in the DM ED + SDF-1 eMSC group. BM-MSCs, especially SDF-1 eMSCs, improved ED (p < 0.05). SDF-1 eMSC treatment improved the smooth muscle content in the corpus cavernosum (p < 0.05). As SDF-1 expression increased, ED recovery improved. In the SDF-1 eMSC group, levels of neuronal nitric oxide synthase (nNOS) and phosphorylated endothelial NOS (p-eNOS) were higher than those in other groups (p < 0.05). In addition, high stromal cell-derived factor-1 (SDF-1) expression was associated with increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in DM ED rats (p < 0.05). Higher levels of phosphorylated protein kinase B (p-AKT)/protein kinase B (AKT) (p < 0.05) and B-cell lymphoma-2 (Bcl-2) and lower levels of the apoptosis factors Bcl2-associated x (Bax) and caspase-3 were observed in the MSC-treated group than in the DM ED group (p < 0.05). SDF-1 eMSCs showed beneficial effects on recovery from erectile function.

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“…CNI induces neurapraxia, decreased NOS, smooth muscle apoptosis, and penile fibrosis, which result in erectile dysfunction. Although the exact mechanism of ADSC therapy remains unclear, ADSCs have shown a paracrine effect on surrounding smooth muscle, neurons, and endothelium to promote regeneration (10). To elucidate the mechanisms of ADSCs in improving erectile function, a study tracked ADSCs after injection in a CNI rat model using 5-ethynyl-2-deoxyuridine-labeled ADSCs.…”

Section: Discussionmentioning

confidence: 99%

Adipose Tissue-Derived Stem Cell Therapy for Cavernous Nerve Injury-Induced Erectile Dysfunction in the Rat Model: A Systematic Review and Meta-Analysis Using Methodological Quality Assessment

Park

Jeong

Park

et al. 2019

IJSC

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Background and Objectives Few studies were evaluated the effect of blindness on outcome in animal models, though a potential effect of blinding has been reported in clinical trials. We evaluated the effects of adipose tissue-derived stem cells (ADSCs) on cavernous nerve injury (CNI)-induced erectile dysfunction (ED) in the rat and examined how proper blinding of the outcome assessor affected treatment effect. Methods and Results We searched in Pubmed, EMBASE, Cochrane and Web of Science databases from inception to January 2019. We included CNI animal model, randomized controlled experiments, and ADSC intervention. Erectile function and structural changes were assessed by intracavernous pressure and mean arterial pressure (ICP/MAP) ratios, neuronal nitric oxide synthase (nNOS) levels, cavernous smooth muscle and collagen (CSM/collagen) ratios, and cyclic guanosine monophosphate (cGMP). Results Nineteen studies were included in the final meta-analysis. The ICP/MAP ratio of the ADSC treatment group increased compared to the control group (SMD=1.33, 95%CI: 1.11~1.56, I 2 =72%). The nNOS level (SMD=2.29, 95%CI: 1.74~2.84, I 2 =75%), CSM/collagen (SMD=2.57, 95%CI: 1.62~3.52; I 2 =85%), and cGMP (SMD=2.96, 95%CI: 1.82~4.10, I 2 =62%) were also increased in the ADSC treatment group. Preplanned subgroup analysis was conducted to explore the source of heterogeneity. Five studies with blinded outcome assessment were significantly less effective than the unblinded studies (SMD=1.33, 95%CI: 0.86~1.80; SMD=1.81, 95%CI: 1.17~2.46, respectively). Conclusions ADSCs might be effective in improving erectile function and structural change in CNI-induced ED. However, non-blinded outcome assessors might cause detection bias and overestimate treatment efficacy. Therefore, the ADSC efficacy must be further evaluated with a rigorous study design to avoid bias.

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Current Perspectives on Stem Cell Therapy for Erectile Dysfunction

Cited by 29 publications

References 73 publications

Co‐overexpression of VEGF and GDNF in adipose‐derived stem cells optimizes therapeutic effect in neurogenic erectile dysfunction model

Co‐overexpression of VEGF and GDNF in adipose‐derived stem cells optimizes therapeutic effect in neurogenic erectile dysfunction model

Engineered Mesenchymal Stem Cells Expressing Stromal Cell-derived Factor-1 Improve Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats

Adipose Tissue-Derived Stem Cell Therapy for Cavernous Nerve Injury-Induced Erectile Dysfunction in the Rat Model: A Systematic Review and Meta-Analysis Using Methodological Quality Assessment

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