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The efficacy of human testicular stromal cell and neuronal precursor cell in a mouse model of cavernous nerve injury

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Sources of Funding: Basic Science Research Program (Young Researcher Program) through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning((NRF-2015R1C1A1A02037466)

Introduction

To investigated the efficacy of newly developed human testicular stromal cell (TSC) and neuronal precursor cell (NPC) for erectile function in a mouse model of cavernous nerve crushed injury (CNI)

Methods

Twelve-week-old NOD-SCID mice were divided into eight groups: sham operation group, bilateral CNI group receiving a single intracavernous injection of phosphate-buffered saline (20 μL), TSC1 (3 × 105 cells/20 μL) or TSC2 (6 × 105 cells/20 μL), NPC1 (3 × 105 cells/20 μL) or NPC2 (6 × 105 cells/20 μL), TSC+NPC combination(3 × 105 cells, each, in total 20 μL), ADMSC2 (6 × 105 cells/20 μL) or oral sildenafil group (5mg/kg). 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. All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) at our institution.

Results

Significant improvement in erectile function was observed in the TSC2 and TSC+ NPC group which reached 29.8% and 38.1% of the sham control value, respectively (p<0.05). Both in immunohistochemistry and Western blot analysis, TSC2 and TSC+NPC group showed significantly increased expression of cavernous endothelial (PECAM-1, eNOS) and smooth muscle content (α-SMA). NPC2 and TSC+NPC group showed significantly increased expression of neurofilament content in the cavernosum tissue or dorsal nerve bundle (Neurofilament). TSC+NPC combination group showed significant recovery in both functional and molecular levels compared with the single cell treated group. Also the TSC+ NPC combination showed superior results than ADMSC2 or Sildenafil groups.

Conclusions

This is the first study to investigate the efficacy of newly developed TSC and NPC for erectile dysfunction in CNI mouse model. The combination of TSC and NPC successfully restored erectile function in CNI mice by restoring endothelial, smooth muscle, and neuronal content.

Funding

Basic Science Research Program (Young Researcher Program) through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning((NRF-2015R1C1A1A02037466)

Authors
Kyung Hwa Choi
Byeong Seong Ki
Seung Ryeol Lee
Young Kwon Hong
Dong Soo Park
Dong Ryul Lee
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