Regeneration of pathological pulmonary vascular bed by endothelial progenitor cell transplantation

目标：1；内皮祖细胞移植是否可行？诱导病理性肺血管床阻塞或发育不良的解剖和功能再生？2. 病理肺移植EPC的最佳方法是什么？方法：(1)8 ~ 10周龄雌性B6小鼠腹腔注射MCT 80mg/kg。(2)注射MCT 4周后，取其他小鼠股骨和胫骨的1 × 10^6/0.2ml单核细胞1注入眼眶静脉。(3)单核细胞移植后4周，处死小鼠，观察肺血管床新生血管的形成情况。检测肺动脉数、肺动脉内侧厚度（估计内侧厚度/血管直径）和右心室肌重量（估计右心室肌重量/室间隔和左心室肌重量）。结果：(1)肺动脉数；对照组为5.0±2.0。MNC移植组为17±3.6。(2)内侧厚度；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，移植组为0.21±0.02。讨论：MNC移植组肺动脉数目明显增加，中侧壁厚度和右心室肌重量明显减少。这意味着肺动脉高压随着肺新生血管的形成而降低。因此，MNC移植有可能在临床上用于病理性肺血管床阻塞或发育不全的再生。此外，还应评估不同的移植方法，是直接注射到肺组织还是经支气管注射。

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.