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The studies with adipose-derived stem/stromal cells therapeutic development of erectile dysfunction

脂肪干细胞/基质细胞治疗勃起功能障碍的研究进展

基本信息

批准号：
21592066
负责人：
NISHIMATSU Hiroaki
金额：
$ 3万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

INTRODUCTION AND OBJECTIVES : Diabetic patients are more refractory to the treatment with phosphodiesterase type 5 inhibitors(PDE-5I) because of severe damage in their cavernous body. We have previously reported that acute administration of Adrenomedullin(AM) into the cavernous body enhances erectile function in rats. During the screening of cytokines that adipose tissue-derived stem cells(ASC) produce, we found that ASC produced AM especially when ASC were cultured in medium containing growth factors for vascular endothelial cells(VEC). In this study, we examined whether AM would be implicated in ASCinduced restoration of erectile function.METHODS : ASC isolated from the subcutaneous adipose tissue of a Wister rat was cultured for one week in either EBM or EGM medium which contains vascular endothelial cell growth factor such as VEGF-A, IGF with 5% FBS. Streptozotocin(STZ) was injected into a male Wister rat. Stem cells cultured using the two methods above were injected into the corpu … More s spongiosum penis of the model rat and a normal rat in the ninth week after STZ administration. The mean arterial blood pressure(MAP) and the intracavernosal pressure(ICP) were measured. We used lentivirus(LV) expressing rat AM siRNA and AdAM, and examined whether AM produced by ASC played pivotal roles in ASC-induced restoration of erectile function. RESULTS : 1. ASC administration restores ICP ; Administration of ASC significantly increased ICP/MAP and AUC. 2. ASC administration restores the structure of cavernous body ; When ASC were injected, the trabeculae of cavernous body became larger and were distributed more densely. 3. ASC produce AM ; The ASC secreted AM in the culture medium in a time-dependent fashion. When ASC were infected with LV that expresses AM siRNA and cultured for 1 week, AM secretion by ASC was significantly suppressed. 4. Effects of AM knockdown and forced expression of AM ; ASC were infected with LV expressing AM siRNA(LV_AMsiRNA) or its negtive control NC siRNA(LV_NC siRNA), cultured for 1 week, and injected in the cavernous body. When ASC were infected with LV_NC siRNA, ASC significantly restored erectile function, as assessed by ICP/MAP and AUC. In contrast, when ASC were infected with LV_AM siRNA, ASC-induced restoration of ICP/MAP and AUC was significantly diminished. CONCLUSIONS : These results suggested that ASC have potentials to restore erectile function and that AM produced by ASC when cultured especially in EGM plays a major role in the restoration of erectile function Less

简介和目的：糖尿病患者更难用磷酸二酯酶5型抑制剂（PDE-5I）治疗，因为他们的海绵体严重受损。我们以前曾报道过，急性给药肾上腺髓质素（AM）到海绵体增强勃起功能的大鼠。在筛选脂肪组织来源的干细胞（ASC）产生的细胞因子的过程中，我们发现ASC产生AM，尤其是当ASC在含有血管内皮细胞（VEC）生长因子的培养基中培养时。在这项研究中，我们研究是否AM将牵连在ASCinduced recovery of erectile functions.METHODS：ASC分离自Wister大鼠皮下脂肪组织培养一周的EBM或EGM培养基中含有血管内皮细胞生长因子，如VEGF-A，IGF与5%FBS。将链脲佐菌素（STZ）注射到雄性Wister大鼠中。将用上述两种方法培养的干细胞注射到体内， ...更多信息大鼠阴茎海绵体组织病理学观察显示，模型组大鼠阴茎海绵体组织病理学改变明显高于正常组。测量平均动脉压（MAP）和海绵体内压（ICP）。我们使用慢病毒（LV）表达大鼠AM siRNA和AdAM，并检查ASC产生的AM是否在ASC诱导的勃起功能恢复中起关键作用。结果：1. ASC给药可恢复ICP ; ASC给药可显著增加ICP/MAP和AUC。2.注射ASC后海绵体结构恢复，海绵体骨小梁变大，分布更密集。3. ASC产生AM ; ASC在培养基中以时间依赖性方式分泌AM。当用表达AM siRNA的LV感染ASC并培养1周时，ASC的AM分泌被显著抑制。4. AM敲低和AM强制表达的影响：用表达AM的LV siRNA（LV_AMsiRNA）或其连续对照NC siRNA（LV_NC siRNA）感染ASC，培养1周，并注射到海绵体中。当用LV_NC siRNA感染ASC时，ASC显著恢复勃起功能，如通过ICP/MAP和AUC评估的。与此相反，当ASC感染LV_AM siRNA时，ASC诱导的ICP/MAP和AUC的恢复显著减弱。结论：这些结果表明，ASC具有恢复勃起功能的潜力，特别是在EGM中培养时，ASC产生的AM在勃起功能的恢复中起主要作用。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

皮下脂肪由来幹細胞を用いた勃起障害に対する新規細胞治療法の開発

使用皮下脂肪干细胞开发治疗勃起功能障碍的新型细胞疗法

DOI：
发表时间：
2010
期刊：
影响因子：
0
作者：
通讯作者：

【Annual Review腎臓】間質性膀胱炎:最新の知見東京

[肾脏年度回顾]间质性膀胱炎：最新发现东京

DOI：
发表时间：
2011
期刊：
中外医学社
影响因子：
0
作者：
野宮明;本間之夫
通讯作者：
本間之夫

Adrenomedullin Mediates Adipose Tissue-Derived Stem Cell-induced Restoration of Erectile Function in Diabetic Rats

DOI：
10.1111/j.1743-6109.2011.02469.x
发表时间：
2012-02-01
期刊：
JOURNAL OF SEXUAL MEDICINE
影响因子：
3.5
作者：
Nishimatsu, Hiroaki;Suzuki, Etsu;Homma, Yukio
通讯作者：
Homma, Yukio

Association between lower urinary tract symptoms and sexual dysfunction assessed using the core lower urinary tract symptom score and International index of erectile function-5 questionnaires

DOI：
10.3109/13685538.2011.646342
发表时间：
2012-06-01
期刊：
AGING MALE
影响因子：
2.6
作者：
Nakamura, Masaki;Fujimura, Tetsuya;Homma, Yukio
通讯作者：
Homma, Yukio

miR-200b precursor can ameliorate renal tubulointerstitial fibrosis.

DOI：
10.1371/journal.pone.0013614
发表时间：
2010-10-25
期刊：
PloS one
影响因子：
3.7
作者：
Oba S;Kumano S;Suzuki E;Nishimatsu H;Takahashi M;Takamori H;Kasuya M;Ogawa Y;Sato K;Kimura K;Homma Y;Hirata Y;Fujita T
通讯作者：
Fujita T