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静脉输注骨髓间充质干细胞可减轻大鼠海绵体神经损伤后的勃起功能障碍。

Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats.

作者信息

Matsuda Yohei, Sasaki Masanori, Kataoka-Sasaki Yuko, Takayanagi Akio, Kobayashi Ko, Oka Shinichi, Nakazaki Masahito, 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; Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT, USA.

出版信息

Sex Med. 2018 Mar;6(1):49-57. doi: 10.1016/j.esxm.2017.10.005. Epub 2017 Dec 21.

Abstract

INTRODUCTION

Intravenous preload (delivered before cavernous nerve [CN] injury) of bone marrow-derived mesenchymal stem cells (MSCs) can prevent or decrease postoperative erectile dysfunction (J Sex Med 2015;12:1713-1721). In the present study, the potential therapeutic effects of intravenously administered MSCs on postoperative erectile dysfunction were evaluated in a rat model of CN injury.

METHODS

Male Sprague-Dawley rats were randomized into 2 groups after electric CN injury. Intravenous infusion of bone marrow-derived MSCs (1.0 × 10 cells in Dulbecco's modified Eagle's medium 1 mL) or vehicle (Dulbecco's modified Eagle's medium 1 mL) was performed 3 hours after electrocautery-induced CN injury.

MAIN OUTCOME MEASURES

To assess erectile function, we measured intracavernous pressure at 4 weeks after MSC or vehicle infusion. Histologic examinations were performed to investigate neuronal innervation and inhibition of smooth muscle atrophy. Green fluorescent protein-positive bone marrow-derived MSCs were used for cell tracking. To investigate mRNA expression levels of neurotrophins in the major pelvic ganglia (MPGs), quantitative real-time polymerase chain reaction was performed.

RESULTS

The decrease of intracavernous pressure corrected for arterial pressure and area under the curve of intracavernous pressure in the bone marrow-derived MSC group was significantly lower than that in the vehicle group at 4 weeks after infusion (P < .05). Retrograde neuronal tracing indicated that the MSC group had a larger number of FluoroGold-positive neurons in the MPGs compared with the vehicle group. The ratio of smooth muscle to collagen in the MSC group was significantly higher than in the vehicle group. Green fluorescent protein-positive bone marrow-derived MSCs were detected in the MPGs and injured CNs using confocal microscopy, indicating homing of cells to the MPGs and injured CNs. Brain-derived neurotrophic factor and glial cell-derived neurotrophic factor expression levels in the MPGs were significantly higher in the MSC group than in the vehicle group (P < .01).

CONCLUSION

Intravenous infusion of bone marrow-derived MSCs after CN injury might have therapeutic efficacy in experimental erectile dysfunction. Matsuda Y, Sasaki M, Kataoka-Sasaki Y, et al. Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats. Sex Med 2018;6:49-57.

摘要

引言

骨髓间充质干细胞(MSCs)静脉预负荷(在海绵体神经[CN]损伤前给予)可预防或减轻术后勃起功能障碍(《性医学杂志》2015年;12:1713 - 1721)。在本研究中,在大鼠CN损伤模型中评估了静脉注射MSCs对术后勃起功能障碍的潜在治疗效果。

方法

雄性Sprague - Dawley大鼠在电刺激致CN损伤后随机分为2组。在电灼诱导的CN损伤后3小时,静脉输注骨髓来源的MSCs(1.0×10个细胞于1 mL Dulbecco改良 Eagle培养基中)或赋形剂(1 mL Dulbecco改良 Eagle培养基)。

主要观察指标

为评估勃起功能,我们在输注MSCs或赋形剂4周后测量海绵体内压。进行组织学检查以研究神经支配和抑制平滑肌萎缩。绿色荧光蛋白阳性的骨髓来源MSCs用于细胞追踪。为研究主要盆腔神经节(MPGs)中神经营养因子的mRNA表达水平,进行了定量实时聚合酶链反应。

结果

输注后4周,骨髓来源MSCs组经动脉压校正的海绵体内压降低以及海绵体内压曲线下面积均显著低于赋形剂组(P <.05)。逆行神经追踪表明,与赋形剂组相比,MSCs组MPGs中FluoroGold阳性神经元数量更多。MSCs组平滑肌与胶原蛋白的比例显著高于赋形剂组。使用共聚焦显微镜在MPGs和损伤的CNs中检测到绿色荧光蛋白阳性的骨髓来源MSCs,表明细胞归巢至MPGs和损伤的CNs。MSCs组MPGs中脑源性神经营养因子和胶质细胞源性神经营养因子的表达水平显著高于赋形剂组(P <.01)。

结论

CN损伤后静脉输注骨髓来源的MSCs可能对实验性勃起功能障碍具有治疗效果。松田洋、佐佐木正、片冈佐纪等。静脉输注骨髓间充质干细胞可减轻大鼠海绵体神经损伤后的勃起功能障碍。《性医学》2018年;6:49 - 57。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0631/5815969/21811559f606/gr1.jpg

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