中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2008年
11期
1004-1008
,共5页
祁春梅%马根山%刘乃丰%陈忠%沈成兴%刘孝钧%胡耀鹏%苏亚民%李璇%张晓黎%滕皋军%居胜红
祁春梅%馬根山%劉迺豐%陳忠%瀋成興%劉孝鈞%鬍耀鵬%囌亞民%李璇%張曉黎%滕皋軍%居勝紅
기춘매%마근산%류내봉%진충%침성흥%류효균%호요붕%소아민%리선%장효려%등고군%거성홍
心肌梗死%干细胞移植%磁共振成像
心肌梗死%榦細胞移植%磁共振成像
심기경사%간세포이식%자공진성상
Myocardial infarction%Stem cells transplantation%Magnetic resonance imaging
目的 骨髓单个核细胞(BM-MNC)及骨髓间质干细胞(MSC)经磁探针标记后,应用磁共振成像(MRI)观察磁探针标记的BM-MNC(MR-MNC)及MSC(MR-MSC)治疗猪急性心肌梗死(AMI)的疗效.方法 24头小型家猪经皮冠状动脉介入法成功制备AMI模型19头,随机分为MR-MSC组(n=7)、MR-MNC组(n=6)和AMI对照组(n=6),分别经冠状动脉途径植入MR-MSC、MR-MNC(细胞总数1×107)和含菲立磁标记物的磷酸盐缓冲液,MRI爪踪移植细胞并观察8周后不同细胞类型移植对梗死心肌面积及心功能的影响,最后行组织学检查鉴定移植细胞及其功能.结果 MRI示MR-MSC组、MR-MNC组均见呈低信号的标记细胞归巢至呈高信号的梗死心肌区周边或梗死心肌内.与移植前相比,8周后MRI测定梗死心肌而积在标记细胞移植组均明显缩小(MR-MSC组8.5%±0.5%比24.7%±3.1%,P＜0.05;MR-MNC组12.3%±1.5%比26.1%±1.5%,P＜0.05);左室射血分数(LVEF)均有明显提高(MR-MSC组56.9%±1.3%比40.7%±2.0%,P＜0.05;MR-MNC组52.8%±1.4%比41.9%±3.3%,P＜0.05),但MR-MSC组LVEF改善程度优于MR-MNC组(16.2%±1.2%比10.9%±3.0%,P＜0.05).普鲁士蓝染色证实标记细胞分布与MRI所见低信号区分布基本一致.Western blot分析显示心肌再生指标肌球蛋白重链表达在MR-MSC组(100.3±5.5)及MR-MNC组(95.5±4.2)均高于AMI对照组(75.7±5.7);心肌特异性肌钙蛋白T在MR-MSC组(124.0±5.8)及MR-MNC组(118.4±4.4)均高于AMI组(93.3±3.9);心肌重构指标基质金属蛋白酶2(MMP2)/MMP抑制剂1(TIMP1)在MR-MSC组(0.6±0.1)及MR-MNC组(0.6±0.1)低于AMI对照组(4.2±0.2).结论 MR-MSC及MR-MNC可在体分化成表达心肌特异性蛋白的心肌样细胞,延缓心室重构,缩小梗死心肌面积,改善整体心窒收缩功能,且MR-MSC对心功能改善程度优于MR-MNC.
目的 骨髓單箇覈細胞(BM-MNC)及骨髓間質榦細胞(MSC)經磁探針標記後,應用磁共振成像(MRI)觀察磁探針標記的BM-MNC(MR-MNC)及MSC(MR-MSC)治療豬急性心肌梗死(AMI)的療效.方法 24頭小型傢豬經皮冠狀動脈介入法成功製備AMI模型19頭,隨機分為MR-MSC組(n=7)、MR-MNC組(n=6)和AMI對照組(n=6),分彆經冠狀動脈途徑植入MR-MSC、MR-MNC(細胞總數1×107)和含菲立磁標記物的燐痠鹽緩遲液,MRI爪蹤移植細胞併觀察8週後不同細胞類型移植對梗死心肌麵積及心功能的影響,最後行組織學檢查鑒定移植細胞及其功能.結果 MRI示MR-MSC組、MR-MNC組均見呈低信號的標記細胞歸巢至呈高信號的梗死心肌區週邊或梗死心肌內.與移植前相比,8週後MRI測定梗死心肌而積在標記細胞移植組均明顯縮小(MR-MSC組8.5%±0.5%比24.7%±3.1%,P＜0.05;MR-MNC組12.3%±1.5%比26.1%±1.5%,P＜0.05);左室射血分數(LVEF)均有明顯提高(MR-MSC組56.9%±1.3%比40.7%±2.0%,P＜0.05;MR-MNC組52.8%±1.4%比41.9%±3.3%,P＜0.05),但MR-MSC組LVEF改善程度優于MR-MNC組(16.2%±1.2%比10.9%±3.0%,P＜0.05).普魯士藍染色證實標記細胞分佈與MRI所見低信號區分佈基本一緻.Western blot分析顯示心肌再生指標肌毬蛋白重鏈錶達在MR-MSC組(100.3±5.5)及MR-MNC組(95.5±4.2)均高于AMI對照組(75.7±5.7);心肌特異性肌鈣蛋白T在MR-MSC組(124.0±5.8)及MR-MNC組(118.4±4.4)均高于AMI組(93.3±3.9);心肌重構指標基質金屬蛋白酶2(MMP2)/MMP抑製劑1(TIMP1)在MR-MSC組(0.6±0.1)及MR-MNC組(0.6±0.1)低于AMI對照組(4.2±0.2).結論 MR-MSC及MR-MNC可在體分化成錶達心肌特異性蛋白的心肌樣細胞,延緩心室重構,縮小梗死心肌麵積,改善整體心窒收縮功能,且MR-MSC對心功能改善程度優于MR-MNC.
목적 골수단개핵세포(BM-MNC)급골수간질간세포(MSC)경자탐침표기후,응용자공진성상(MRI)관찰자탐침표기적BM-MNC(MR-MNC)급MSC(MR-MSC)치료저급성심기경사(AMI)적료효.방법 24두소형가저경피관상동맥개입법성공제비AMI모형19두,수궤분위MR-MSC조(n=7)、MR-MNC조(n=6)화AMI대조조(n=6),분별경관상동맥도경식입MR-MSC、MR-MNC(세포총수1×107)화함비립자표기물적린산염완충액,MRI조종이식세포병관찰8주후불동세포류형이식대경사심기면적급심공능적영향,최후행조직학검사감정이식세포급기공능.결과 MRI시MR-MSC조、MR-MNC조균견정저신호적표기세포귀소지정고신호적경사심기구주변혹경사심기내.여이식전상비,8주후MRI측정경사심기이적재표기세포이식조균명현축소(MR-MSC조8.5%±0.5%비24.7%±3.1%,P＜0.05;MR-MNC조12.3%±1.5%비26.1%±1.5%,P＜0.05);좌실사혈분수(LVEF)균유명현제고(MR-MSC조56.9%±1.3%비40.7%±2.0%,P＜0.05;MR-MNC조52.8%±1.4%비41.9%±3.3%,P＜0.05),단MR-MSC조LVEF개선정도우우MR-MNC조(16.2%±1.2%비10.9%±3.0%,P＜0.05).보로사람염색증실표기세포분포여MRI소견저신호구분포기본일치.Western blot분석현시심기재생지표기구단백중련표체재MR-MSC조(100.3±5.5)급MR-MNC조(95.5±4.2)균고우AMI대조조(75.7±5.7);심기특이성기개단백T재MR-MSC조(124.0±5.8)급MR-MNC조(118.4±4.4)균고우AMI조(93.3±3.9);심기중구지표기질금속단백매2(MMP2)/MMP억제제1(TIMP1)재MR-MSC조(0.6±0.1)급MR-MNC조(0.6±0.1)저우AMI대조조(4.2±0.2).결론 MR-MSC급MR-MNC가재체분화성표체심기특이성단백적심기양세포,연완심실중구,축소경사심기면적,개선정체심질수축공능,차MR-MSC대심공능개선정도우우MR-MNC.
Objective To evaluate the therapeutic effects of magnetically labeled mononuclear stem cells (MR-MNC) and mesenchymal stem cells (MR-MSC) transplantation in a swine acute myocardial infarction (AMI) model by MR imaging.Methods AMI model was established in swines by balloon occlusion of the left anterior descending coronary artery,107 autologous MR-MSC (n=7),MR-MNC (n=6) or PBS(n=6) were delivered via intracoronary infusion within 1 week after AMI [(4.8±1.3) days].Changes of infarct size and cardiac function were assessed with the use of 3.0T MR scanner before AMI,at 1 and 8 weeks post AMI.Results Magnetically labeled stem cells could be identified in the region of AMI by cardiac MR imaging.Eight weeks post transplantation,infarct size was significantly reduced in MR-MSC transplantation group(8.5%±0.5% vs.24.7%±3.1%,P＜0.05) and in MR-MNC transplantation (12.3%±1.5% vs.26.1%±1.5%,P＜0.05) while infaret size remained unchanged in PBS group (P＞0.05) compared to values at 1 week post AMI,left yentricular ejection fraction (LVEF) was also significantly higher in MR-MSC transplantation group (56.9%±1.3% vs.40.7%±2.0%,P＜0.05) and MR-MNC transplantation group (52.8%±1.4% vs.41.9%±3.3%,P＜0.06) compared to LVEF at 1 week post AML LVEF increase was more significant in swines received MR-MSC transplantation than MRMNC transplantation(16.2%±1.2% vs.10.9%±3.0%,P＜0.05).Prussian blue staining identified stem cells in corresponding myocardial regions with as by MRI.Western blot analysis demonstrated that cardiac expressions of myosin heavy chain (MHC) in MR-MSC group (100.3±5.5) and in MR-MNCs group (95.5±4.2) were significantly higher than that in PBS group (75.7±5.7,P＜0.05),myocardial troponin T (cTNT) expression in MR-MSC group (124.0±5.8) and MR-MNC group (118.4±4.4) were also significantly higher than in PBS group (93.3±3.9,P＜0.05) while MMP2/TIMP1 ratios in MR-MSC group (0.6±0.1) and MR-MNC group (0.6±0.1) were significandy lower than that in PBS group (4.2±0.2,P＜0.05).Conclusions Magnetically labeled MR-MSC and MR-MNC homed to heart post myocardial infarction and reduced infarct size,improved cardiac function.MR-MSC is superior to MR-MNC on improving cardiac function.
