A study of urinary tissue remodeling by modulating the homing mechanism of bone marrow derived cells

调节骨髓来源细胞归巢机制的泌尿组织重塑研究

基本信息

批准号：
18591737
负责人：
MORIYA Kimihiko
金额：
$ 2.35万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591737/
关键词：
Bone marrow derived cells Urinary tissue remodeling

项目摘要

Objectives: We investigated the time course of the stromal cell-derived factor 1a (SDF1α) expression and behavior of intravenously administered bone-marrow derived stromal (MDS) cells in the urinary bladder of partial bladder outlet obstruction (PBOO) rats.Material and Methods: Study 1: Recombinant SDF1α or saline was directly injected into bladder wall of female rats followed by intravenous administration of MDS cells isolated from GFP transgenic rats, and the bladder was examined with immunohistochemistry. Study 2: Following surgery of PBOO or Sham in female rats, the bladder was exposed on Dayl, 3, 7, 10 and 14, and expression of hypoxia inducible factor la (HIF1α) and SDF1α were examined with real-time PCR. Study 3: Female rats underwent PBOO or Sham surgery followed by intravenous administration of GFP rats' MDS cells, and the bladder was examined with immunohistochemistry on Day1 and 14.Results: In the bladder with injection of SDF1 a, not saline, MDS cells were accumulated in the injection site of the bladder (Study 1). SDF1α and HIF1α increased and peaked on Day1 after PBOO compared to Sham (Study 2). More MDS cells were accumulated in the bladder of PBOO on Day1 as well as Day14, and some cells differentiated into smooth muscle phenotypes on Day 14 (Study 3).Conclusions: SDF1α induced with ischemia/hypoxia due to PBOO is implicated in homing of MDS cells to the bladder. Intravenous administration of MDS cells could have a potential to be an attractive cell therapy for the bladder dysfunction in bladder outlet obstruction.

目的：我们研究了在部分Bladeder出口对象（PBOO）的尿腔（PBOO）的尿中，静脉内施用的骨头（MDS）细胞静脉内施用的骨头（MDS）细胞（PBOO）的骨骼（MDS）细胞的表达和行为的时间过程和行为。从GFP转基因大鼠中分离出的MDS细胞的静脉注射，并检查了膀胱以免疫组织化学检查。研究2：在雌性大鼠的PBOO或假手术后，在Dayl，3、7、10和14上暴露了膀胱，并用实时PCR检查了缺氧诱导因子LA（HIF1α）和SDF1α的表达。研究3：雌性大鼠接受了PBOO或假手术，然后进行静脉内给予GFP大鼠的MDS细胞，并在第1天和14.囊肿检查膀胱以免疫组织化学检查：在膀胱中注射SDF1 A，非盐碱细胞，盐碱细胞，MDS细胞在囊囊的注射部位中积累了MDS细胞（研究1）。与假相比，SDF1α和HIF1α在PBOO后的第1天增加并达到峰值（研究2）。在第1天和第14天，在PBOO的膀胱中积累了更多的MDS细胞，在第14天，一些细胞分化为平滑肌表型（研究3）。结论：Conconconions：通过PBOO引起的缺血/缺氧诱导的SDF1α暗示在MDS细胞将MDS细胞归为Blader中。 MDS细胞的静脉内给药可能是膀胱出口阻塞中膀胱功能障碍的有吸引力的细胞疗法。