Int J Stem Cells.  2019 Jul;12(2):206-217. 10.15283/ijsc18122.

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 HJ
• Jeong H
• Park YH
• Yim HW
• Ha US
• Hong SH
• Kim SW
• Kim NJ
• Lee JY

• KMID: 2465892
• DOI: http://doi.org/10.15283/ijsc18122

Abstract

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, I²=72%). The nNOS level (SMD=2.29, 95%CI: 1.74~2.84, I²=75%), CSM/collagen (SMD=2.57, 95%CI: 1.62~3.52; I²=85%), and cGMP (SMD=2.96, 95%CI: 1.82~4.10, I²=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.

Keyword

Adipose tissue-derived stem cell; Erectile dysfunction; Meta-analysis

MeSH Terms

Animals
Arterial Pressure
Bias (Epidemiology)
Blindness
Collagen
Erectile Dysfunction*
Guanosine Monophosphate
Male
Models, Animal*
Muscle, Smooth
Nitric Oxide Synthase Type I
Population Characteristics
Rats*
Stem Cells*
Treatment Outcome
Collagen
Guanosine Monophosphate
Nitric Oxide Synthase Type I

Figure

• 

  Fig. 1 Flow diagram of the studies included in the meta-analysis.

• 

  Fig. 2 ADSC effects on erectile function and structural change. (A) Intracavernous pressure and mean arterial pressure (ICP/MAP) ratio, (B) neuronal nitric oxide synthase (nNOS), (C) cavernous smooth muscle and collagen (CSM/collagen) ratio, and (D) cyclic guanosine monophosphate (cGCMP).

• 

  Fig. 3 Contour enhanced funnel plots displaying discrepancy between published data and after imputing studies estimated to be missing from the funnel plot asymmetry. Publication bias. (A) Unadjusted contour enhanced funnel plot and (B) adjusted contour enhanced funnel plot.

Reference

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