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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
International Journal of Stem Cells
Published online April 30, 2019;  
© 2019 Korean Society for Stem Cell Research.

Hyo Jung Park1,2, Hyunsuk Jeong3,*, Yong Hyun Park1, Hyeon Woo Yim3, U-syn Ha1, Sung-Hoo Hong1, Sae Woong Kim1, Na Jin Kim4, Ji Youl Lee1,2,*

1Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea
2Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Korea
3Department of Preventive Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
4Medical Library, The Catholic University of Korea, Seoul, Korea
Correspondence to: Ji Youl Lee
Department of Urology, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
Tel: +82-2-2258-6227, Fax: +82-2-2258-1536, E-mail:
Co-Correspondence to Hyunsuk Jeong
Department of Preventive Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
Tel: +82-2-2258-7372, Fax: +82-2-532-3820, E-mail:
*These authors contributed equally to this work.
Received November 29, 2018; Revised February 9, 2019; Accepted February 11, 2019.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords : Adipose tissue-derived stem cell, Erectile dysfunction, Meta-analysis