脐带源间充质干细胞促进造血细胞在NOD/SCID小鼠归巢  

Human Umbilical Cord Derived Mesenchymal Stem Cells Augment Human Hematopoietic Cell Homing and Engraftment into the NOD/SCID Mouse

作　　者：张浪辉[1,2] 陈志哲[1] 吕璐璐[1,2] 王爱萍[2] 韩忠朝[2] 刘拥军[2] 

机构地区：[1]福建医科大学附属协和医院血液科,福建省血液病研究所,福州350001 [2]泰达国家干细胞中心,中国医学科学院血液学研究所,天津300020

出　　处：《福建医科大学学报》2006年第3期203-206,共4页Journal of Fujian Medical University

基　　金：国家863计划(2003AA205060);973重大基础研究项目(001CB5101);国家自然科学基金资助项目(30570905)

摘　　要：目的探讨脐带源间充质干细胞(hUC-MSC)在促进造血细胞归巢,提高造血干细胞植入中的作用。方法RT-PCR检测经体外培养扩增所得hUC-MSC归巢相关分子的表达;将hUC-MSC和CFDA-SE荧光标记的人脐带血单个核细胞(MNC)植入NOD/SCID小鼠建立共移植模型,分离共移植24h后小鼠骨髓有核细胞,用流式细胞仪和荧光倒置显微镜观察脐带血造血细胞在NOD/SCID小鼠骨髓中含量的变化。结果hUC-MSC表达SDF-1及其受体CXCR-4以及相关黏附分子CD11a/ICAM-1、CD49d/VCAM-1;在hUC-MSC共移植情况下,流式细胞仪检测和荧光显微镜下细胞计数均发现人脐带血MNC在小鼠骨髓中的含量与单独脐带血移植相比较有显著提高〔(145±59)/1×105vs(298±72)/1×105;(755±158)/5×105vs(1598±227)/5×105个骨髓有核细胞;n=9,P<0.05)〕。结论hUC-MSC具有表达化学趋化因子及相关黏附分子的特性,有利于实现自身的归巢定位并引导造血干祖细胞的有效归巢与植入;动物模型的建立进一步证实其引导脐带血MNC在NOD/SCID小鼠体内向造血龛———骨髓富集(归巢)的作用。Objective To study the role of mesenchymal stem cells（hUC-MSC） derived from human umbilical cord on the homing and engraftment of hematopoietic stem/progenitor cells in cotransplantation. Methods RT-PCR technique was used to detect the expression of chemokine and adhesion molecules of hUC-MSC. A co-transplantation of hUC-MSC conducted into nonobese diabetic/severe combined immundeficicency（NOD/SCID） mouse model was developed to detect the variation of human hematopoietic cells homing in bone marrow by fluorescent microscope and FCM technique. Results hUC-MSCs expression of chemokine receptor CXCR-4, stromal derived factor （SDF-1）, and other adhesion molecules CDlla/ICAM-1, CD49d /VCAM-1 were identified by RT-PCR. Cotransplantation of hUC-MSC from umbilical cord blood（UCB） resulted a significant increment of human UCB mononuclear cells（MNC） in NOD/SCID mouse bone marrow as compared with the infusion of UCB alone [（145±59）/1 ×10^5 vs （298± 72）/1×10^5;（755±158）/5×10^5 vs （1598±227）/5×10^5,n=9, P〈0.05）]. Conclusion hUC-MSCcan express chemokine and associated adhesion molecules which would do favor to themselves homing as well as augment homing and engraftment of hematopoietic stem/progenitor cells. The outcome of NOD/SCID mouse model of cotransplantation confirmed that hUC-MSC could promote the migration and accumulation of umbilical cord blood MNC in NOD/SCID mouse hematopoietic niche-bone marrow（homing）, which should be the indication for hUC-MSC cotransplantation in clinical hematopoietic stem cell transplatantions.

关 键 词：间充质干细胞 脐带 造血干细胞 受体 淋巴细胞归巢 移植 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]