静脉注射间充质干细胞可挽救海绵体神经损伤大鼠模型的勃起功能。

Intravenous Preload of Mesenchymal Stem Cells Rescues Erectile Function in a Rat Model of Cavernous Nerve Injury.

作者信息

Takayanagi Akio, Sasaki Masanori, Kataoka-Sasaki Yuko, Kobayashi Ko, Matsuda Yohei, Oka Shinichi, Masumori Naoya, Kocsis Jeffery D, Honmou Osamu

机构信息

Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.

出版信息

J Sex Med. 2015 Aug;12(8):1713-21. doi: 10.1111/jsm.12957. Epub 2015 Jul 24.

DOI:10.1111/jsm.12957

PMID:26211660

Abstract

INTRODUCTION

We evaluated the potential preventive effects and mechanisms of intravenously preloaded mesenchymal stem cells (MSCs) for erectile dysfunction (ED) in a cavernous nerve (CN) injury model.

METHODS

Male Sprague-Dawley (SD) rats were used for this study. Rats were randomized into two groups. One group was intravenously preloaded with MSCs (1.0 × 10(6) cells in 1 mL total fluid volume) and the other was infused with medium alone (1 mL Dulbecco's modified Eagle's medium [DMEM]) for sham control, respectively. Crushed CN injury was induced immediately after infusion. The surgeon was blind to the experimental conditions (MSC or medium).

MAIN OUTCOME MEASURES

To assess erectile function, we measured the intracavernous pressure (ICP) and arterial pressure (AP) at 1 hour and 2 weeks after CN injury. After measuring the initial ICP/AP of pre-injury (normal) male SD rats, they were randomized into the two groups and infused with MSCs or medium. PKH26-labelled MSCs were used for tracking. To investigate the mRNA expression levels of neurotrophins in the major pelvic ganglia (MPG), we performed real-time quantitative real-time polymerase chain reaction.

RESULTS

The reduction of ICP/AP and area under the curve of ICP (ICP-AUC) in the MSC group was significantly lower than in the DMEM group (P < 0.05; P < 0.05) at 1 hour. The ICP/AP and ICP-AUC at 2 weeks post-injury in the MSC group was significantly higher than in the DMEM group (P < 0.01; P < 0.05). The preloaded PKH26-labelled MSCs were detected in the MPG and CN using confocal microscopy indicating homing of the cells to the injured nerve and ganglia. Glia cell-derived neurotrophic factor (GDNF) and neurturin, which are important neurotrophic factors for erection, had expression levels in MPG significantly higher in the MSC group than in the DMEM group (P < 0.01, 0.05).

CONCLUSION

Intravenous preload of MSCs before a CN injury may prevent or reduce experimental ED.

摘要

引言

我们在海绵体神经（CN）损伤模型中评估了静脉预加载间充质干细胞（MSC）对勃起功能障碍（ED）的潜在预防作用及机制。

方法

本研究采用雄性Sprague-Dawley（SD）大鼠。大鼠被随机分为两组。一组静脉预加载MSC（1.0×10⁶个细胞，总体积1 mL），另一组仅输注培养基（1 mL Dulbecco改良 Eagle培养基[DMEM]）作为假对照。输注后立即诱导海绵体神经挤压损伤。手术医生对实验条件（MSC或培养基）不知情。

主要观察指标

为评估勃起功能，我们在海绵体神经损伤后1小时和2周测量海绵体内压（ICP）和动脉压（AP）。在测量损伤前（正常）雄性SD大鼠的初始ICP/AP后，将它们随机分为两组并输注MSC或培养基。使用PKH26标记的MSC进行追踪。为研究主要盆腔神经节（MPG）中神经营养因子的mRNA表达水平，我们进行了实时定量聚合酶链反应。

结果

在1小时时，MSC组的ICP/AP降低以及ICP曲线下面积（ICP-AUC）显著低于DMEM组（P<0.05；P<0.05）。损伤后2周时，MSC组的ICP/AP和ICP-AUC显著高于DMEM组（P<0.01；P<0.05）。使用共聚焦显微镜在主要盆腔神经节和海绵体神经中检测到预加载的PKH26标记的MSC，表明细胞归巢至损伤的神经和神经节。胶质细胞源性神经营养因子（GDNF）和神经营养素是勃起的重要神经营养因子，其在主要盆腔神经节中的表达水平在MSC组显著高于DMEM组（P<0.01，0.05）。