一、不同心脏状态下心梗边缘区注射骨髓间充质干细胞的比较 二、体外循环和停跳的心脏状态对于经冠状动脉内移植骨髓间充质干细胞的影响
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摘要
第一部分:不同心脏状态下心梗边缘区注射骨髓间充质干细胞的比较
目的:
细胞移植是目前缺血性心脏病治疗研究的热点之一。干细胞治疗心肌梗塞已被证明是种很有前途的治疗方法。细胞移植在体内的存留、分布、迁移除了受移植途径影响外,心脏的状态也会影响移植细胞的归宿。本实验主要研究停跳与不停跳两种心脏状态下,经猪心梗模型心肌注射骨髓间充质干细胞后全身细胞的分布情况。
方法:实验方法分为体内和体外实验两部分
体外实验部分:从雄性中华小型猪髂骨处抽取骨髓,体外培养扩增骨髓间充质干细胞并进行鉴定。将超顺磁氧化铁颗粒和骨髓间充质干细胞共同孵育培养36-48小时。使用普鲁士蓝染色评价标记后的细胞铁离子标记的效率;使用台盼蓝染色检验标记后细胞的活性。
体内实验部分:用带球囊血管造影导管经股动脉导入雌性猪左冠状动脉前降支,在第二对角支的近端将球囊扩张90分钟造成急性心梗模型。模型建立后7天随机分为四组。第1组为停跳心脏细胞注射组(n=6),体外循环后心脏停跳,标记的细胞(1×10~8)经心肌注入心梗周边区。第2组为不停跳心脏细胞注射组(n=6),相同的细胞在跳动下心脏经心肌注入心梗周边区。第3组停跳心脏对照组(n=6)和第4组不停跳心脏对照组(n=6)中,相同剂量的生理盐水分别在停跳和不停跳心脏状态下经心肌注入心梗周边区。3天后,体内细胞分布通过核磁共振的T2*变化及雄性细胞特异性的SRY基因的实时定量PCR检测来评价。并取动物心,肝,脾,肺,肾的标本,切片后进行普鲁士蓝染色,观察细胞在体内的分布和形态。
结果
体外实验部分:
普鲁士兰染色的超顺磁铁纳米颗粒标记的骨髓间充质干细胞显示,蓝染的铁的小囊泡或小颗粒分布于几乎每个细胞的胞浆中,其标记效率几乎达到100%。并且,在台盼兰排斥实验中,95%以上的细胞拒染台盼兰,可见骨髓间充质干细胞经铁标记后有良好的活性。
体内实验部分:
细胞可以在心,脾,肺和肝中检测到。1,2组中大部分的注射细胞滞留在心脏,并目1组中心脏细胞的滞留较2组多(T2*改变:22.3±2.2 versus 17.00±0.84;SRY gene:0.150±0.062 versus 0.072±0.003)。病理学检查可以见移植细胞呈普鲁士蓝染色阳性,并与磁共振影像学的显影有很好的一致性。
结论:
经心肌注射骨髓间充质干细胞后,许多细胞流向心脏以外的器官,尤其是脾脏。在心脏停跳状态下经心肌注射骨髓间充质干细胞将更有利于细胞在心脏的滞留,在开胸手术中是一种最适合的细胞移植方法。
第二部分:体外循环和停跳的心脏状态对于经冠状动脉内移植骨髓间充质细胞后细胞的存留、分布的影响
目的:
冠状动脉内细胞移植是目前临床细胞移植的主要途径,冠状动脉内细胞移植后移植细胞的存留、分布和迁移是关系细胞移植治疗效果的重要因素之一。体外循环和停跳的心脏状态是心脏外科手术常用的方式,本实验主要比较停跳与不停跳两种心脏状态下经冠脉注射骨髓间充质干细胞后移植细胞在心脏内的存留、分布和迁移情况以及在全身重要脏器内的分布。
方法:
雄性猪的骨髓间充质干细胞用超顺磁铁纳米颗粒标记。雌性猪心梗后一周随机分为四组。第1组为跳动心脏细胞注射组(n=6),标记的细胞(1×10~8)经左前降支冠脉注入跳动的心脏。第2组为停跳心脏细胞注射组(n=6),体外循环建立,心脏停跳后,相同的细胞经左前降支注入。第3组跳动心脏对照组(n=6)和第4组停跳心脏对照组(n=6)中,相同剂量的生理盐水分别在不停跳和停跳心脏状态下经冠脉注入心脏。3天后,体内细胞分布通过核磁共振的T2*变化及Y染色体性别决定区基因(SRY基因)的实时定量PCR检测来评价。
结果:
细胞可以在心,肝,脾,肺和肾中检测到。1,2组中一小部分的注射细胞滞留在心脏,但两组比较没有统计学差异。大量的细胞滞留在心脏外脏器中,尤以停跳细胞移植组脾脏中较多。1组中移植细胞的凋亡比率较2组少,在细胞移植后3天未发现有肌样分化表现。
结论:
经冠脉移植细胞后大量的细胞将滞留在心外器官脾脏中,停跳心脏对于冠脉移植干细胞并无明显意义。最适宜的间充质干细胞的移植方式仍需进一步探索。
Objective:
Stem cell therapy has emerged as a promising approach for the treatment of myocardial infarction(MI).The transplanted cell's retention, migration is affected not only by the transplanted approach,but also by the heart status.This preclinical study was to test the intramyocardially injected bone marrow(BM) mesenchymal stem cells(MSCs) cell distribution in different heart statues(arresting or beating) in a porcine myocardial infarction (MI) model.
Methods:
In vitro study:
BM was aspirated from the iliac crest of male swine.Bone marrow MSCs were expanded and incubated with SPIO for 48 hours.The labeling efficiency was tested through Prussian blue staining,and cells viability was tested through Trypan blue rejection method.
In vivo study:
An occlusive angioplasty balloon was advanced into the proximal left anterior descending coronary artery via percutaneous approach.Acute MI was induced by inflating the balloon for 90 minutes followed by artery perfusion.1 week after creation of MI in female swine,the survivals were randomly divided into 4 groups.Cardiopulmonary bypass was set up to arrest heart,and then labeled cells(1×10~8) were intramyocardially injected into the borderline of infracted zone in Group 1(n=6).Same volumes of cells were grafted in the beating heart in Group 2(n=6).In Group 3 and 4,the same volume of saline was injected in either arresting or beating heart(n=6 respectively).3 days later,cell distribution was assessed by T2~* change with magnetic resonance imaging and sex-determining region on Y-chromosome (SRY) with quantitive polymerase chain reaction.The interested segment of heart,liver,spleen,lung,and kidney tissues were collected for Prussian Blue Staining.
Results:
In vitro study:
Prussian blue staining of SPIO-labeled MSCs revealed the presence of numerous blue staining iron-containing vesicles or particles in the cytoplasm of nearly every cell.The labeling efficiency reached approximately 100%.More than 95%labeled cells were not stained with Trypan Blue.
In vivo study:
The cells were identified in heart,spleen,lung and liver.Most of injected cells were localized in the myocardium in Group 1 and 2,however, the amount of detained cells was much higher in Group 1(T2~* change: 22.3±2.2 versus 17.00±0.84;SRY gene:0.150±0.062 versus 0.072±0.003). The injected sites containing labeled cells could all be detected through MRI and were confirmed on pathology.
Conclusion:
Even after intramyocardially injection,many cells migrated to extracardiac organs especially to the spleen.Our results indicated injection in the arresting heart could favor more cells be retained in myocardium and thus it was an optimal approach to deliver MSCs during open chest surgery.
Backgroud:
Transcorocnary infusion of the therapeutic stem cells is the most popular delivery approach of cell transplantation to improve cardiac function for the injured heart,but few data is reported about the retention,distribution, and migration of the implanted cells.Systemic distribution of bone marrow stromal cells(BMSCs) after intracoronary infusion(ICI) and the role of cardiopulmonary bypass(CPB) in cell distribution still remain unclear.This study was designed o analyze the cell distribution after ICI in variations of heart status in a swine myocardial infarction(MI) model.
Methods:
After inducing an MI,iron oxide labeled male cells(1×10~8) were infused through the coronary artery of the beating swine heart in Group 1.In group 2,CPB was set up and then the same volume of cells was infused after cadioplegic arrest.In Group 3 and 4,the animals underwent either beating or arrested ICI with the same volume of saline.Three days later,cell distribution was assessed by T2~* change with magnetic resonance imaging and sex-determining region on Y-chromosome with quantitive polymerase chain reaction.
Results:
Only a few transplanted cells were localized in the heart and no difference was found between groups 1 and 2.The majority of BMSCs would be trapped in extracardial organs,and more cells resided in the spleen in arrested heart status.The percentage of the apoptotic cells in the implanted cells in Group 1 was lower than that in Group 2.Expression of the muscle-specific markers wasn't observed at 3 days in Prussian blue-positive cells.
Conclusion:
The majority of BMSCs transplanted by ICI would be entrapped by the extracardial organs.The arrested heart with CPB during ICI does not favor more cells retention in the injured myocardium.The optimal approach of delivery of BMSCs still needs further investigation.
目的:
细胞移植是目前缺血性心脏病治疗研究的热点之一。干细胞治疗心肌梗塞已被证明是种很有前途的治疗方法。细胞移植在体内的存留、分布、迁移除了受移植途径影响外,心脏的状态也会影响移植细胞的归宿。本实验主要研究停跳与不停跳两种心脏状态下,经猪心梗模型心肌注射骨髓间充质干细胞后全身细胞的分布情况。
方法:实验方法分为体内和体外实验两部分
体外实验部分:从雄性中华小型猪髂骨处抽取骨髓,体外培养扩增骨髓间充质干细胞并进行鉴定。将超顺磁氧化铁颗粒和骨髓间充质干细胞共同孵育培养36-48小时。使用普鲁士蓝染色评价标记后的细胞铁离子标记的效率;使用台盼蓝染色检验标记后细胞的活性。
体内实验部分:用带球囊血管造影导管经股动脉导入雌性猪左冠状动脉前降支,在第二对角支的近端将球囊扩张90分钟造成急性心梗模型。模型建立后7天随机分为四组。第1组为停跳心脏细胞注射组(n=6),体外循环后心脏停跳,标记的细胞(1×10~8)经心肌注入心梗周边区。第2组为不停跳心脏细胞注射组(n=6),相同的细胞在跳动下心脏经心肌注入心梗周边区。第3组停跳心脏对照组(n=6)和第4组不停跳心脏对照组(n=6)中,相同剂量的生理盐水分别在停跳和不停跳心脏状态下经心肌注入心梗周边区。3天后,体内细胞分布通过核磁共振的T2*变化及雄性细胞特异性的SRY基因的实时定量PCR检测来评价。并取动物心,肝,脾,肺,肾的标本,切片后进行普鲁士蓝染色,观察细胞在体内的分布和形态。
结果
体外实验部分:
普鲁士兰染色的超顺磁铁纳米颗粒标记的骨髓间充质干细胞显示,蓝染的铁的小囊泡或小颗粒分布于几乎每个细胞的胞浆中,其标记效率几乎达到100%。并且,在台盼兰排斥实验中,95%以上的细胞拒染台盼兰,可见骨髓间充质干细胞经铁标记后有良好的活性。
体内实验部分:
细胞可以在心,脾,肺和肝中检测到。1,2组中大部分的注射细胞滞留在心脏,并目1组中心脏细胞的滞留较2组多(T2*改变:22.3±2.2 versus 17.00±0.84;SRY gene:0.150±0.062 versus 0.072±0.003)。病理学检查可以见移植细胞呈普鲁士蓝染色阳性,并与磁共振影像学的显影有很好的一致性。
结论:
经心肌注射骨髓间充质干细胞后,许多细胞流向心脏以外的器官,尤其是脾脏。在心脏停跳状态下经心肌注射骨髓间充质干细胞将更有利于细胞在心脏的滞留,在开胸手术中是一种最适合的细胞移植方法。
第二部分:体外循环和停跳的心脏状态对于经冠状动脉内移植骨髓间充质细胞后细胞的存留、分布的影响
目的:
冠状动脉内细胞移植是目前临床细胞移植的主要途径,冠状动脉内细胞移植后移植细胞的存留、分布和迁移是关系细胞移植治疗效果的重要因素之一。体外循环和停跳的心脏状态是心脏外科手术常用的方式,本实验主要比较停跳与不停跳两种心脏状态下经冠脉注射骨髓间充质干细胞后移植细胞在心脏内的存留、分布和迁移情况以及在全身重要脏器内的分布。
方法:
雄性猪的骨髓间充质干细胞用超顺磁铁纳米颗粒标记。雌性猪心梗后一周随机分为四组。第1组为跳动心脏细胞注射组(n=6),标记的细胞(1×10~8)经左前降支冠脉注入跳动的心脏。第2组为停跳心脏细胞注射组(n=6),体外循环建立,心脏停跳后,相同的细胞经左前降支注入。第3组跳动心脏对照组(n=6)和第4组停跳心脏对照组(n=6)中,相同剂量的生理盐水分别在不停跳和停跳心脏状态下经冠脉注入心脏。3天后,体内细胞分布通过核磁共振的T2*变化及Y染色体性别决定区基因(SRY基因)的实时定量PCR检测来评价。
结果:
细胞可以在心,肝,脾,肺和肾中检测到。1,2组中一小部分的注射细胞滞留在心脏,但两组比较没有统计学差异。大量的细胞滞留在心脏外脏器中,尤以停跳细胞移植组脾脏中较多。1组中移植细胞的凋亡比率较2组少,在细胞移植后3天未发现有肌样分化表现。
结论:
经冠脉移植细胞后大量的细胞将滞留在心外器官脾脏中,停跳心脏对于冠脉移植干细胞并无明显意义。最适宜的间充质干细胞的移植方式仍需进一步探索。
Objective:
Stem cell therapy has emerged as a promising approach for the treatment of myocardial infarction(MI).The transplanted cell's retention, migration is affected not only by the transplanted approach,but also by the heart status.This preclinical study was to test the intramyocardially injected bone marrow(BM) mesenchymal stem cells(MSCs) cell distribution in different heart statues(arresting or beating) in a porcine myocardial infarction (MI) model.
Methods:
In vitro study:
BM was aspirated from the iliac crest of male swine.Bone marrow MSCs were expanded and incubated with SPIO for 48 hours.The labeling efficiency was tested through Prussian blue staining,and cells viability was tested through Trypan blue rejection method.
In vivo study:
An occlusive angioplasty balloon was advanced into the proximal left anterior descending coronary artery via percutaneous approach.Acute MI was induced by inflating the balloon for 90 minutes followed by artery perfusion.1 week after creation of MI in female swine,the survivals were randomly divided into 4 groups.Cardiopulmonary bypass was set up to arrest heart,and then labeled cells(1×10~8) were intramyocardially injected into the borderline of infracted zone in Group 1(n=6).Same volumes of cells were grafted in the beating heart in Group 2(n=6).In Group 3 and 4,the same volume of saline was injected in either arresting or beating heart(n=6 respectively).3 days later,cell distribution was assessed by T2~* change with magnetic resonance imaging and sex-determining region on Y-chromosome (SRY) with quantitive polymerase chain reaction.The interested segment of heart,liver,spleen,lung,and kidney tissues were collected for Prussian Blue Staining.
Results:
In vitro study:
Prussian blue staining of SPIO-labeled MSCs revealed the presence of numerous blue staining iron-containing vesicles or particles in the cytoplasm of nearly every cell.The labeling efficiency reached approximately 100%.More than 95%labeled cells were not stained with Trypan Blue.
In vivo study:
The cells were identified in heart,spleen,lung and liver.Most of injected cells were localized in the myocardium in Group 1 and 2,however, the amount of detained cells was much higher in Group 1(T2~* change: 22.3±2.2 versus 17.00±0.84;SRY gene:0.150±0.062 versus 0.072±0.003). The injected sites containing labeled cells could all be detected through MRI and were confirmed on pathology.
Conclusion:
Even after intramyocardially injection,many cells migrated to extracardiac organs especially to the spleen.Our results indicated injection in the arresting heart could favor more cells be retained in myocardium and thus it was an optimal approach to deliver MSCs during open chest surgery.
Backgroud:
Transcorocnary infusion of the therapeutic stem cells is the most popular delivery approach of cell transplantation to improve cardiac function for the injured heart,but few data is reported about the retention,distribution, and migration of the implanted cells.Systemic distribution of bone marrow stromal cells(BMSCs) after intracoronary infusion(ICI) and the role of cardiopulmonary bypass(CPB) in cell distribution still remain unclear.This study was designed o analyze the cell distribution after ICI in variations of heart status in a swine myocardial infarction(MI) model.
Methods:
After inducing an MI,iron oxide labeled male cells(1×10~8) were infused through the coronary artery of the beating swine heart in Group 1.In group 2,CPB was set up and then the same volume of cells was infused after cadioplegic arrest.In Group 3 and 4,the animals underwent either beating or arrested ICI with the same volume of saline.Three days later,cell distribution was assessed by T2~* change with magnetic resonance imaging and sex-determining region on Y-chromosome with quantitive polymerase chain reaction.
Results:
Only a few transplanted cells were localized in the heart and no difference was found between groups 1 and 2.The majority of BMSCs would be trapped in extracardial organs,and more cells resided in the spleen in arrested heart status.The percentage of the apoptotic cells in the implanted cells in Group 1 was lower than that in Group 2.Expression of the muscle-specific markers wasn't observed at 3 days in Prussian blue-positive cells.
Conclusion:
The majority of BMSCs transplanted by ICI would be entrapped by the extracardial organs.The arrested heart with CPB during ICI does not favor more cells retention in the injured myocardium.The optimal approach of delivery of BMSCs still needs further investigation.
引文
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21. Zhou R, Acton PD, Ferrari VA. Imaging stem cells implanted in infarcted myocardium. J Am Coll Cardiol 2006;48(10):2094-106.
22. Penicka M, Widimsky P, Kobylka P, Kozak T, Lang O. Images in cardiovascular medicine. Early tissue distribution of bone marrow mononuclear cells after transcoronary transplantation in a patient with acute myocardial infarction. Circulation 2005;112(4):e63-5.
23. Hou D, Youssef EA, Brinton TJ, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 2005;l 12(9 Suppl):1150-6.
24. He G, Zhang H, Wei H, et al. In vivo imaging of bone marrow mesenchymal stem cells transplanted into myocardium using magnetic resonance imaging: a novel method to trace the transplanted cells. Int J Cardiol 2007; 114(1):4-10.
25. van den Bos EJ, Baks T, Moelker AD, et al. Magnetic resonance imaging of haemorrhage within reperfused myocardial infarcts: possible interference with iron oxide-labelled cell tracking? Eur Heart J 2006;27(13): 1620-6.
26. Lee TH, Reed W, Mangawang-Montalvo L, Watson J, Busch MP. Donor WBCs can persist and transiently mediate immunologic function in a murine transfusion model:effects of irradiation, storage, and histocompatibility. Transfusion 2001 ;41 (5):637-42.
27. Freyman T, Polin G, Osman H, et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J 2006;27(9):1114-22.
28. Barbash IM, Chouraqui P, Baron J, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 2003;108(7):863-8.
29. Stamm C, Kleine HD, Choi YH, et al. lntramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease:safety and efficacy studies. J Thorac Cardiovasc Surg 2007;133(3):717-25.
30. Menasche P, Hagege AA, Vilquin JT, et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 2003;41(7):1078-83.
31. Teng CJ, Luo J, Chiu RC, Shum-Tim D. Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: implications for cellular cardiomyoplasty. J Thorac Cardiovasc Surg 2006;132(3):628-32.
32. Dai W, Hale SL, Martin BJ, et al. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation 2005;112(2):214-23.
1. Massie BM, Shah NB. Evolving trends in the epidemiologic factors of heart failure: rational for preventive strategies and comprehensive disease management. Am Heart J 1997; 133: 703-712.
2. Massie BM, Shah NB. The heart failure epidemic: magnitude of the problem and potential mitigating approaches. Curr Opin Cardiol 1996; 11: 221-226.
3. Assmus B, Scha-Chinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI).Circulation 2002; 106:3009-17.
4. Blau HM, Brazelton TR, Weimann JM, et al. The evolving concept of a stem cell:entity or function? Cell 2001; 105:829-41.
5. Fuchs E, Sergre JA. Stem cells: a new lease on life. Cell 2000; 100:143-55.
6. Kuehnle I, Goodell MA. The therapeutic potential of stem cells from adults. Br Med J 2002;325:372-6.
7. Dawn B, Stein AB, Urbanek KU, et al. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infracted myocardium and improve cardiac function.Proc NatlAcad Scien 2005;102:3766-71.
8. Wang JS, Shun-Tim D, Chedrawy E, et al. The coronary delivery of marrow stromal cells for myocardial regeneration: pathophysiologic and therapeutic implications. J Thorac Cardiovascu Surg 2001;112:699-705.
9. Saito T, Kuang JQ, Lin CCH, et al. Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction. J Thorac Cardiovascu Surg 2003; 126:114-123.
10. Vicario J, Campos C, Faccio P F, et al. Trancocoronary sinus administration of autologous bone marrow in patients with chronic stable angina: phase 1. Cardiovascu Radiation Medicine 5(2004):71-76.
11. Vicario J, Piva J, Pierini A, et al. Transcoronary sinus delivery of autologous bone marrow and angiogenesis in pig models with myocardial injury. Cardiovascu Radiation Medicine 2003; 3:91-94.
12. Fuchs S, Salter LF, Konorwski R, et al. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol 2003;41:1721-4.
13. Carot J, Unterseeh T, Teiger E, et al. Magnetic resonance imaging of targeted catheter-based implantation of myogenic precursor cells into infracted left ventricular myocardium. J Am Coll Cardiol 2003 ;41:1841 -6.
14. Smit PC, M van Geuns R J, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure.J Am Coll Cardiol 2003;42:2063-9
15. Thompson C A, Nasseri B A, Makower J, et al. Percutaneous transvenous cellular cardiomyoplasty : a novel nonsurgical approach for myocardial cell transplantation. J Am Coll Cardiol 2003;41:1964-71
16. Siminiak T, Fiszer D, Jerzykowska O, et al. Percutaneous autologous myoblast transplantation in the treatment of post-infarction myocardial contractility impairment -report on two cases. Polish Heart Journal 2003;59: 12.
17. Bos C, Delmas Y, Desmouliere A, et al. In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. Radiology 2004;233(3):781-9.
18.Dawn, B., et al., Cardiac stem ceils delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci U S A, 2005. 102(10): p. 3766-71.
19. Hou D, Youssef EA, Brinton TJ, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 2005;l 12:1150-6.
20.Gao, J, et al, The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs, 2001. 169(1): p. 12-20.
21.Chisholm PM, Danpure HJ, Healey G, et al. Cell damaging result from the labeling of rat lymphocyte and HeLa S3 cells with In-111 oxine. J Nucl Med. 1979;20;1308-11.
22.Cui J, Wahl RL, Shen T, et al. Bone marrow cell trafficking following intravenous adiminstration. Br J Haematol. 1999;107:895-902.
23.Ciulla MM, Lazzari L, Pacchiana R, et al. Homing of peripherally injected bone marrow cells in rat after experimental myocardial injury. Heamatologica.2003;88:614-621.
24. Hofmann, M., et al., Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation, 2005. 111(17): p. 2198-202.
25. Penicka, M., et al, Images in cardiovascular medicine. Early tissue distribution of bone marrow mononuclear cells after transcoronary transplantation in a patient with acute myocardial infarction. Circulation, 2005. 112(4): p. e63-5.
26. Dai W, Hale SL, Martin BJ, et al. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation 2005:112:214-23.
1.朱洪生等.骨髓间质干细胞移植对香猪急性心肌梗死后心肌结构和心功能的影响.中国胸心血管外科临床杂志,2004,11(2):112-115.
2.Strauer BE,Brehm M,Zeus T,et al.Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans.Circulation,2002,106(15):1913-1918.
3.Wu JC,Chen IY,Sundaresan G,et al.Molecular imaging of cardiac cell transplantation in living animals using optical bioluminescence and positron emission tomography.Circulation,2003,108(11):1302-1305.
4.Maggi A,Ciana P.Reporter mice and drug discovery and development.Nat Rev Drug Discov,2005,4(3):249-255.
5.Wang X,Rosol M,Ge S,et al.Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging.Blood,2003,102(10):3478-3482.
6.Rudin M,Rausch M,Stoeckli M.Molecular imaging in drug discovery and development:potential and limitations of nonnuclear methods.Mol Imaging Biol,2005,7(1):5-13.
7.Thompson M,Wall DM,Hicks R J,et al.In vivo tracking for cell therapies.Q J Nucl Med Mol Imaging,2005,49(4):339-348.
8.Chemaly ER,Yoneyama R,Frangioni JV,et al.Tracking stem cells in the cardiovascular system.Trends Cardiovasc Med,2005,15(8):297-302.
9.Hofmann M,Wollert KC,Meyer GP.et al.Monitoring of bone marrow cell homing into the infarcted human myocardium.Circulation,2005,111(17):2198-2202.
10.Kang W J,Kang H J,Kim HS,et al.Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. J Nucl Med, 2006, 47(8): 1295-1301.
11.Barbash IM, Chouraqui P, Baron J, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation, 2003, 108(7): 863-868.
12.Penicka M, Widimsky P, Kobylka P, et al. Images in cardiovascular medicine.Early tissue distribution of bone marrow mononuclear cells after transcoronary transplantation in a patient with acute myocardial infarction. Circulation, 2005, 112(4):e63-65.
13.Chin BB, Nakamoto Y, Bulte JW, et al. 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction. Nucl Med Commun,2003,24(11): 1149-1154.
14.Hou D, Youssef EA, Brinton TJ, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery:implications for current clinical trials. Circulation, 2005, 112(9 Suppl): 1150-156.
15.Stodilka RZ, Blackwood KJ, Prato FS. Tracking transplanted cells using dual-radionuclide SPECT. Phys Med Biol, 2006, 51(10): 2619-2632.
16.Kraitchman DL, Tatsumi M, Gilson WD, et al. Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation, 2005, 112(10):1451-1461.
17.Kraitchman DL, Heldman AW, Atalar E, et al. In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation, 2003, 107(18):2290-2293.
18.Amado LC, Saliaris AP, Schuleri KH, et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A, 2005, 102(32): 11474-11479.
19.Hill JM, Dick AJ, Raman VK, et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation, 2003, 108(8): 1009-1014.
20.Bos C, Delmas Y, Desmouliere A, et al. In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. Radiology,2004, 233(3): 781-789.
21.Daldrup-Link HE, Rudelius M, Oostendorp RA, et al. Targeting of hematopoietic progenitor cells with MR contrast agents. Radiology, 2003, 228(3): 760-767.
22.Kostura L, Kraitchman DL, Mackay AM, et al. Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed,2004, 17(7): 513-517.
23.Terrovitis JV, Bulte JW, Sarvananthan S, et al. Magnetic Resonance Imaging of Ferumoxide-Labeled Mesenchymal Stem Cells Seeded on Collagen Scaffolds-Relevance to Tissue Engineering. Tissue Eng, 2006.
24.Corti R, Badimon J, Mizsei G, et al. Real time magnetic resonance guided endomyocardial local delivery. Heart, 2005, 91(3): 348-353.
25.Arbab AS, Bashaw LA, Miller BR, et al. Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonance imaging after cell transplantation: methods and techniques. Transplantation, 2003, 76(7): 1123-1130.
26.Saito T, Kuang JQ, Lin CC, et al. Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction. J Thorac Cardiovasc Surg,2003, 126(1): 114-123.
27.Cavazzana-Calvo M, Thrasher A, Mavilio F. The future of gene therapy. Nature,2004, 427(6977): 779-781
2. Oh H, Bradfute SB, Gallardo TD, et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A 2003;100(21):12313-8.
3. Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003;114(6):763-76.
4. Messina E, De Angelis L, Frati G, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 2004;95(9):911-21.
5. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001;410(6829):701-5.
6. Schachinger V, Assmus B, Britten MB, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol 2004;44(8): 1690-9.
7. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002; 106(15):1913-8.
8. Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial.Lancet 2004;364(9429):141-8.
9. Murry CE, Soonpaa MH, Reinecke H, et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004;428(6983):664-8.
10. Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC.Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium.Nature 2004;428(6983):668-73.
11. Nygren JM, Jovinge S, Breitbach M, et al. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nat Med 2004;10(5):494-501.
12. Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD.Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs.Lancet 2004;363(9411):783-4.
13. Amado LC, Schuleri KH, Saliaris AP, et al. Multimodality noninvasive imaging demonstrates in vivo cardiac regeneration after mesenchymal stem cell therapy. J Am Coll Cardiol 2006;48(10):2116-24.
14. Hill JM, Dick AJ, Raman VK, et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation 2003; 108(8): 1009-14.
15. Bos C, Delmas Y, Desmouliere A, et al. In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. Radiology 2004;233(3):781-9.
16. Yasuda T, Weisel RD, Kiani C, Mickle DA, Maganti M, Li RK. Quantitative analysis of survival of transplanted smooth muscle cells with real-time polymerase chain reaction. J Thorac Cardiovasc Surg 2005;129(4):904-11.
17. Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 2004;95(1):9-20.
18. Chen SL, Fang WW, Ye F, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol 2004;94(1):92-5.
19. Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ. Stromal cell-derived factor-1 alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury.Circulation 2004;110(21):3300-5.
20. Kraitchman DL, Tatsumi M, Gilson WD, et al. Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 2005;112(10):1451-61.
21. Zhou R, Acton PD, Ferrari VA. Imaging stem cells implanted in infarcted myocardium. J Am Coll Cardiol 2006;48(10):2094-106.
22. Penicka M, Widimsky P, Kobylka P, Kozak T, Lang O. Images in cardiovascular medicine. Early tissue distribution of bone marrow mononuclear cells after transcoronary transplantation in a patient with acute myocardial infarction. Circulation 2005;112(4):e63-5.
23. Hou D, Youssef EA, Brinton TJ, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 2005;l 12(9 Suppl):1150-6.
24. He G, Zhang H, Wei H, et al. In vivo imaging of bone marrow mesenchymal stem cells transplanted into myocardium using magnetic resonance imaging: a novel method to trace the transplanted cells. Int J Cardiol 2007; 114(1):4-10.
25. van den Bos EJ, Baks T, Moelker AD, et al. Magnetic resonance imaging of haemorrhage within reperfused myocardial infarcts: possible interference with iron oxide-labelled cell tracking? Eur Heart J 2006;27(13): 1620-6.
26. Lee TH, Reed W, Mangawang-Montalvo L, Watson J, Busch MP. Donor WBCs can persist and transiently mediate immunologic function in a murine transfusion model:effects of irradiation, storage, and histocompatibility. Transfusion 2001 ;41 (5):637-42.
27. Freyman T, Polin G, Osman H, et al. A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction. Eur Heart J 2006;27(9):1114-22.
28. Barbash IM, Chouraqui P, Baron J, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 2003;108(7):863-8.
29. Stamm C, Kleine HD, Choi YH, et al. lntramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease:safety and efficacy studies. J Thorac Cardiovasc Surg 2007;133(3):717-25.
30. Menasche P, Hagege AA, Vilquin JT, et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 2003;41(7):1078-83.
31. Teng CJ, Luo J, Chiu RC, Shum-Tim D. Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: implications for cellular cardiomyoplasty. J Thorac Cardiovasc Surg 2006;132(3):628-32.
32. Dai W, Hale SL, Martin BJ, et al. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation 2005;112(2):214-23.
1. Massie BM, Shah NB. Evolving trends in the epidemiologic factors of heart failure: rational for preventive strategies and comprehensive disease management. Am Heart J 1997; 133: 703-712.
2. Massie BM, Shah NB. The heart failure epidemic: magnitude of the problem and potential mitigating approaches. Curr Opin Cardiol 1996; 11: 221-226.
3. Assmus B, Scha-Chinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI).Circulation 2002; 106:3009-17.
4. Blau HM, Brazelton TR, Weimann JM, et al. The evolving concept of a stem cell:entity or function? Cell 2001; 105:829-41.
5. Fuchs E, Sergre JA. Stem cells: a new lease on life. Cell 2000; 100:143-55.
6. Kuehnle I, Goodell MA. The therapeutic potential of stem cells from adults. Br Med J 2002;325:372-6.
7. Dawn B, Stein AB, Urbanek KU, et al. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infracted myocardium and improve cardiac function.Proc NatlAcad Scien 2005;102:3766-71.
8. Wang JS, Shun-Tim D, Chedrawy E, et al. The coronary delivery of marrow stromal cells for myocardial regeneration: pathophysiologic and therapeutic implications. J Thorac Cardiovascu Surg 2001;112:699-705.
9. Saito T, Kuang JQ, Lin CCH, et al. Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction. J Thorac Cardiovascu Surg 2003; 126:114-123.
10. Vicario J, Campos C, Faccio P F, et al. Trancocoronary sinus administration of autologous bone marrow in patients with chronic stable angina: phase 1. Cardiovascu Radiation Medicine 5(2004):71-76.
11. Vicario J, Piva J, Pierini A, et al. Transcoronary sinus delivery of autologous bone marrow and angiogenesis in pig models with myocardial injury. Cardiovascu Radiation Medicine 2003; 3:91-94.
12. Fuchs S, Salter LF, Konorwski R, et al. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol 2003;41:1721-4.
13. Carot J, Unterseeh T, Teiger E, et al. Magnetic resonance imaging of targeted catheter-based implantation of myogenic precursor cells into infracted left ventricular myocardium. J Am Coll Cardiol 2003 ;41:1841 -6.
14. Smit PC, M van Geuns R J, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure.J Am Coll Cardiol 2003;42:2063-9
15. Thompson C A, Nasseri B A, Makower J, et al. Percutaneous transvenous cellular cardiomyoplasty : a novel nonsurgical approach for myocardial cell transplantation. J Am Coll Cardiol 2003;41:1964-71
16. Siminiak T, Fiszer D, Jerzykowska O, et al. Percutaneous autologous myoblast transplantation in the treatment of post-infarction myocardial contractility impairment -report on two cases. Polish Heart Journal 2003;59: 12.
17. Bos C, Delmas Y, Desmouliere A, et al. In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. Radiology 2004;233(3):781-9.
18.Dawn, B., et al., Cardiac stem ceils delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci U S A, 2005. 102(10): p. 3766-71.
19. Hou D, Youssef EA, Brinton TJ, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials. Circulation 2005;l 12:1150-6.
20.Gao, J, et al, The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs, 2001. 169(1): p. 12-20.
21.Chisholm PM, Danpure HJ, Healey G, et al. Cell damaging result from the labeling of rat lymphocyte and HeLa S3 cells with In-111 oxine. J Nucl Med. 1979;20;1308-11.
22.Cui J, Wahl RL, Shen T, et al. Bone marrow cell trafficking following intravenous adiminstration. Br J Haematol. 1999;107:895-902.
23.Ciulla MM, Lazzari L, Pacchiana R, et al. Homing of peripherally injected bone marrow cells in rat after experimental myocardial injury. Heamatologica.2003;88:614-621.
24. Hofmann, M., et al., Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation, 2005. 111(17): p. 2198-202.
25. Penicka, M., et al, Images in cardiovascular medicine. Early tissue distribution of bone marrow mononuclear cells after transcoronary transplantation in a patient with acute myocardial infarction. Circulation, 2005. 112(4): p. e63-5.
26. Dai W, Hale SL, Martin BJ, et al. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation 2005:112:214-23.
1.朱洪生等.骨髓间质干细胞移植对香猪急性心肌梗死后心肌结构和心功能的影响.中国胸心血管外科临床杂志,2004,11(2):112-115.
2.Strauer BE,Brehm M,Zeus T,et al.Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans.Circulation,2002,106(15):1913-1918.
3.Wu JC,Chen IY,Sundaresan G,et al.Molecular imaging of cardiac cell transplantation in living animals using optical bioluminescence and positron emission tomography.Circulation,2003,108(11):1302-1305.
4.Maggi A,Ciana P.Reporter mice and drug discovery and development.Nat Rev Drug Discov,2005,4(3):249-255.
5.Wang X,Rosol M,Ge S,et al.Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging.Blood,2003,102(10):3478-3482.
6.Rudin M,Rausch M,Stoeckli M.Molecular imaging in drug discovery and development:potential and limitations of nonnuclear methods.Mol Imaging Biol,2005,7(1):5-13.
7.Thompson M,Wall DM,Hicks R J,et al.In vivo tracking for cell therapies.Q J Nucl Med Mol Imaging,2005,49(4):339-348.
8.Chemaly ER,Yoneyama R,Frangioni JV,et al.Tracking stem cells in the cardiovascular system.Trends Cardiovasc Med,2005,15(8):297-302.
9.Hofmann M,Wollert KC,Meyer GP.et al.Monitoring of bone marrow cell homing into the infarcted human myocardium.Circulation,2005,111(17):2198-2202.
10.Kang W J,Kang H J,Kim HS,et al.Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction. J Nucl Med, 2006, 47(8): 1295-1301.
11.Barbash IM, Chouraqui P, Baron J, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation, 2003, 108(7): 863-868.
12.Penicka M, Widimsky P, Kobylka P, et al. Images in cardiovascular medicine.Early tissue distribution of bone marrow mononuclear cells after transcoronary transplantation in a patient with acute myocardial infarction. Circulation, 2005, 112(4):e63-65.
13.Chin BB, Nakamoto Y, Bulte JW, et al. 111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction. Nucl Med Commun,2003,24(11): 1149-1154.
14.Hou D, Youssef EA, Brinton TJ, et al. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery:implications for current clinical trials. Circulation, 2005, 112(9 Suppl): 1150-156.
15.Stodilka RZ, Blackwood KJ, Prato FS. Tracking transplanted cells using dual-radionuclide SPECT. Phys Med Biol, 2006, 51(10): 2619-2632.
16.Kraitchman DL, Tatsumi M, Gilson WD, et al. Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation, 2005, 112(10):1451-1461.
17.Kraitchman DL, Heldman AW, Atalar E, et al. In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation, 2003, 107(18):2290-2293.
18.Amado LC, Saliaris AP, Schuleri KH, et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A, 2005, 102(32): 11474-11479.
19.Hill JM, Dick AJ, Raman VK, et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation, 2003, 108(8): 1009-1014.
20.Bos C, Delmas Y, Desmouliere A, et al. In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. Radiology,2004, 233(3): 781-789.
21.Daldrup-Link HE, Rudelius M, Oostendorp RA, et al. Targeting of hematopoietic progenitor cells with MR contrast agents. Radiology, 2003, 228(3): 760-767.
22.Kostura L, Kraitchman DL, Mackay AM, et al. Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed,2004, 17(7): 513-517.
23.Terrovitis JV, Bulte JW, Sarvananthan S, et al. Magnetic Resonance Imaging of Ferumoxide-Labeled Mesenchymal Stem Cells Seeded on Collagen Scaffolds-Relevance to Tissue Engineering. Tissue Eng, 2006.
24.Corti R, Badimon J, Mizsei G, et al. Real time magnetic resonance guided endomyocardial local delivery. Heart, 2005, 91(3): 348-353.
25.Arbab AS, Bashaw LA, Miller BR, et al. Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonance imaging after cell transplantation: methods and techniques. Transplantation, 2003, 76(7): 1123-1130.
26.Saito T, Kuang JQ, Lin CC, et al. Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction. J Thorac Cardiovasc Surg,2003, 126(1): 114-123.
27.Cavazzana-Calvo M, Thrasher A, Mavilio F. The future of gene therapy. Nature,2004, 427(6977): 779-781