Regeneration of pathological pulmonary vascular bed by endothelial progenitor cell transplantation

内皮祖细胞移植修复病理性肺血管床

• 批准号: 17591473
• 负责人: KITAICHI Takashi
• 金额: $ 2.3万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591473/
• 关键词: pulmonary neovasculaization; mononuclear cell; monocrotaline; pulmonary hypertension; mononuclear cell移植; EPC; Dehydromonocrotaline

Objectives : 1. Is it possible transplantation of endothelial progenitor cell (EPC). induce anatomical and functional regeneration of pathological obstructed or hypoplastic pulmonary vascular bed? 2. What is the best way to transplant the EPC to pathological lung?Methods : (1) Female B6 mouse (8-10 week old) were injected 80mg/kg monocrotalin (MCT) intra-peritonially. (2) 4 weeks after MCT injection, mononuclear cell 1(1 X 10^6/0.2ml) which were extracted from femurs and tibias of other mice was injected into orbital vein. (3) 4 weeks after mononuclear cell (MNC) transplantation, mice were sacrificed to examined neovascularization in pulmonary vascular bed. Pulmonary artery number, medial thickness of pulmonary artery which is estimated medial thickness/ vascular diameter and the weight of right ventricular (RV) muscle which is estimated RV muscle weight/ ventricular septum and left ventricular muscle were examined.Results : (1) Pulmonary artery number; control group was 5.0 ± 2.0. and MNC transplantation group was 17± 3.6. (2) Medial thickness; control group was 0.21± 0.05 and MNC transplantation group was 0.08 ± 0.02. (3) RV weight; control group was 0.29± 0.01 and MNC transplantation group was 0.21 ±0.02.Discussion : Pulmonary artery number significantly increased and medial thickness and RV muscle weight decreased in MNC transplantation group. That mean pulmonary hypertension was decreased by pulmonary neovascularization. So MNC transplantation is possibly utilized in regeneration of pathological obstructed or hypoplastic pulmonary vascular bed clinically. Furthermore, different transplantation methods, that is direct injection to lung tissue or transbronchial injection, should be estimated.

目的：1.内皮祖细胞移植是否可行。诱导病理阻塞或发育不良肺血管床解剖和功能再生？2.将EPC移植到病变肺的最佳方法是什么？方法：（1）8-10周龄雌性B6小鼠腹腔注射野百合碱（MCT）80 mg/kg。(2)MCT注射后4周，将从其他小鼠的股骨和胫骨中提取的单核细胞1（1 X 10^6/0.2ml）注射到眶静脉中。(3)移植后4周处死小鼠，观察肺血管床新生血管形成情况。结果：（1）肺动脉数目：对照组为（5.0 ± 2.0）支，肺动脉中膜厚度（中膜厚度/血管直径）和右心室肌重量（右心室肌重量/室间隔和左心室肌重量）均为正常。MNC移植组为17± 3.6。(2)中膜厚度：对照组为0.21± 0.05，MNC移植组为0.08 ± 0.02。(3)RV重量;对照组为0.29± 0.01，MNC移植组为0.21 ± 0.02。讨论：MNC移植组肺动脉数目明显增加，中膜厚度和RV肌重量明显减少。肺新生血管的形成降低了肺动脉高压。因此，MNC移植有可能用于病理性阻塞或发育不良肺血管床的再生。此外，应评估不同的移植方法，即直接注射到肺组织或经支气管注射。