Intracavernous Delivery of Clonal Mesenchymal Stem Cells Restores Erectile Function in a Mouse Model of Cavernous Nerve Injury

Authors

  • Ji-Kan Ryu MD, PhD,

    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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    • These authors contributed equally to this study.
  • Da-Ham Kim MS,

    1. Translational Research Center, Inha University School of Medicine, Incheon, Korea
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    • These authors contributed equally to this study.
  • Kang Moon Song MS,

    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
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  • TacGhee Yi PhD,

    1. Translational Research Center, Inha University School of Medicine, Incheon, Korea
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  • Jun-Kyu Suh MD, PhD,

    Corresponding author
    1. National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Korea
    • Corresponding Authors: Sun U. Song, PhD, Translational Research Center, Inha University School of Medicine, 7-206, 3rd St, Shinheung-Dong, Jung-Gu, Incheon 400-711, Republic of Korea. Tel: 82-32-890-2460; Fax: 82-32-890-2462; E-mail: sunuksong@inha.ac.kr and Jun-Kyu Suh, MD, PhD, National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine 7-206, 3rd St, Shinheung-Dong, Jung-Gu, Incheon 400-711, Republic of Korea. Tel: 82-32-890-3441; Fax: 82-32-890-3097; E-mail: jksuh@inha.ac.kr

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  • Sun U. Song PhD

    Corresponding author
    1. Translational Research Center, Inha University School of Medicine, Incheon, Korea
    • Corresponding Authors: Sun U. Song, PhD, Translational Research Center, Inha University School of Medicine, 7-206, 3rd St, Shinheung-Dong, Jung-Gu, Incheon 400-711, Republic of Korea. Tel: 82-32-890-2460; Fax: 82-32-890-2462; E-mail: sunuksong@inha.ac.kr and Jun-Kyu Suh, MD, PhD, National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine 7-206, 3rd St, Shinheung-Dong, Jung-Gu, Incheon 400-711, Republic of Korea. Tel: 82-32-890-3441; Fax: 82-32-890-3097; E-mail: jksuh@inha.ac.kr

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Abstract

Introduction

Recently, much attention has focused on stem cell therapy; bone marrow-derived stem cells (BMSCs) are one of the most studied mesenchymal stem cells used in the field of erectile dysfunction (ED). However, a major limitation for the clinical application of stem cell therapy is the heterogeneous nature of the isolated cells, which may cause different treatment outcomes.

Aim

We investigated the effectiveness of mouse clonal BMSCs obtained from a single colony by using subfractionation culturing method (SCM) for erectile function in a mouse model of cavernous nerve injury (CNI).

Methods

Twelve-week-old C57BL/6J mice were divided into four groups: sham operation group, bilateral CNI group receiving a single intracavernous (IC) injection of phosphate-buffered saline (20 μL) or clonal BMSCs (3 × 105 cells/20 μL), and receiving a single intraperitoneal (IP) injection of clonal BMSCs (3 × 105 cells/20 μL).

Main Outcome Measures

The clonal BMSC line was analyzed for cell-surface epitopes by using fluorescence-activated cell sorting and for differentiation potential. Two weeks after CNI and treatment, erectile function was measured by electrically stimulating the cavernous nerve. The penis was harvested for histologic examinations and Western blot analysis.

Results

Clonal BMSCs expressed cell surface markers for mesenchymal stem cells and were capable of differentiating into several lineages, including adipogenic, osteogenic, and chondrogenic cells. Both IC and IP injections of clonal BMSCs significantly restored cavernous endothelial and smooth muscle content, and penile nNOS and neurofilament content in CNI mice. IC injection of clonal BMSCs induced significant recovery of erectile function, which reached 90–100% of the sham control values, whereas IP injection of clonal BMSCs partially restored erectile function.

Conclusion

We established a homogeneous population of mouse clonal BMSCs using SCM; clonal BMSCs successfully restored erectile function in CNI mice. The homogeneous nature of clonal mesenchymal stem cells may allow their clinical applications. Ryu J-K, Kim D-H, Song KM, Yi TG, Suh J-K, and Song SU. Intracavernous delivery of clonal mesenchymal stem cells restores erectile function in a mouse model of cavernous nerve injury. J Sex Med 2014;11:411–423.

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