Effect of intracoronary transplantation of autologous bone marrow-derived mononuclear cells on outcomes of patients with refractory chronic heart failure secondary to ischemic cardiomyopathy

Recent studies have indicated that stem cell implantation increases cardiac function by repairing damaged myocardium. We investigated whether intracoronary transplantation of autologous bone marrow-derived mononuclear cells (BMMCs) confers beneficial effects in patients with refractory chronic heart failure. Twenty-eight patients received standard heart failure medication and BMMC transplantation (BMMC treatment) or standard medication only (controls). BMMCs were harvested from each patient. Clinical manifestations, biochemical assays, rhythm studies, echocardiograms, and positron emission tomograms were recorded. Fourteen patients with cell grafting had symptomatic relief of heart failure within 3 days. Left ventricular ejection fraction increased by 9.2% and 10.5% at 1 week and 3 months after the procedure, respectively, versus baseline (p < 0.01 for the 2 comparisons). Left ventricular end-systolic volume decreased by 30.7% after 3 months (p < 0.01). Brain natriuretic peptide levels at days 3 and 7 after cell infusion significantly decreased by 69.2% and 70.4%, respectively, whereas atrial natriuretic peptide levels increased by 30.1% at day 7. Positron emission tomographic analysis showed a significant increase in cell viability of 10.3% in the infarcted zone. No patient died in the BMMC-treated group at 6-month follow-up. In contrast, heart failure did not improve in any control patient. Left ventricular ejection fraction decreased by 7.2% after 3 months. Two control patients died from heart failure within 6 months. In conclusion, this is the first demonstration in humans that intracoronary BMMC transplantation is a feasible and safe therapeutic strategy to decrease symptoms, increase cardiac function, and possibly prolong life in patients with end-stage heart failure refractory to standard medical therapy.     

外周血干细胞移植治疗老年心肌梗死后心力衰竭患者的疗效及安全性

目的比较冠状动脉内自体外周血干细胞（PBSC）移植治疗老年及非老年心肌梗死后心力衰竭患者的治疗效果与安全性。方法25例心肌梗死后心力衰竭患者,以60岁为界限分为老年组13例,非老年组12例,接受粒细胞集落刺激因子动员后的冠脉内自体PBSC移植（PBSCT）治疗。比较两组患者临床资料、冠状动脉病变及支架植入情况、PBSCT的不良反应及其前后左室形态和心功能变化。结果与非老年组比较,老年组合并高血压病、糖尿病、慢性闭塞病变,多支病变及植入支架数均较多。PBSCT6个月后,两组患者的左室舒张末期内径明显缩小,射血分数明显提高,6min步行距离明显增加,心肌灌注缺损面积均明显缩小。而两组上述参数的术前术后变化比较无显著性差异。结论冠脉内自体PBSCT治疗老年人心肌梗死后心力衰竭,能够改善患者心功能,提高生存质量,安全有效,且效果与非老年组无明显差异。     

Peripheral blood stem cells transplantation in patients with heart failure after myocardial infarction:their efficiency and safety

Objective To compare the efficiency and safety of intracoronary transplantation of peripheral blood stem cells (PBSC) between elderly and younger patients with heart failure after myocardial infarction (MI). Methods Twenty-five patients with heart failure after MI were divided into aged group(≥60 years,n=13) and non-aged group(<60years,n=12)to receive intracoronary PBSC transplantation (PBSCT) following bone marrow cells mobilized by granulocyte colony-stimulating factor(G-CSF). Clinical data including coronary lesion characteristic, left ventricular shape,infarct region area and cardiac function, as well as adverse side effects between the two groups were compared. Left ventricular function was evaluated before and 6 months after the treatment by single photon emission computed tomography(SPECT). Results At 6 months, the left ventricular ejection fraction (LVEF) and 6 minute walk test (6MWT) distance increased, while the left ventricular diastolic diameter (LVDd) decreased significantly in both groups. There were no significant difference between the two groups in absolute change in the cardiac function parameters. Conclusions The present study demonstrated that autologous intracoronary PBSCT might be safe and feasible for both old and younger patients with heart failure after MI and left ventricular function is significantly improved.(J Geriatr Cardiol 2007;4:233-237.)     

Intracoronary bone marrow cell application for terminal heart failure in children

Introduction In spite of tremendous progress in the medical and surgical treatment of children with congenital heart disease and dilated cardiomyopathy achieved during the past few decades, for some children a heart transplant remains the only option. Clinically relevant benefits of intracoronary injection of autologous stem cells on cardiac function and remodelling have been demonstrated in adult patients with acute myocardial infarction. Experience with autologous stem cell therapy in children with severe congenital or acquired pump failure is limited to a small number of case reports. Method and results Between 2006 and 2010, nine severely ill children were treated with intracoronary infusion of autologous bone marrow-derived mononuclear cells as part of a compassionate therapy in our centre. No procedure-related unexpected adverse events occurred. There was one patient on extracorporeal membrane oxygenation who died of haemorrhage unrelated to the procedure; three patients proceeded to heart transplantation once a donor heart became available. The other five patients showed an improvement with respect to New York Heart Association classification (greater than or equal to 1), brain natriuretic peptide serum levels, and ejection fraction. Conclusion Similar to adults, intracoronary injection of autologous bone marrow cell is technically feasible and safe for children. On the basis of our data, we propose to perform a pilot study for children with congestive heart failure, to formally assess the efficacy of intracoronary autologous bone marrow cell therapy.     

Transcoronary Bone Marrow‐Derived Progenitor Cells in a Child With Myocardial Infarction: First Pediatric Experience

Background

Recent advances in stem cell therapy to restore cardiac function have great promise for patients with congestive heart failure after myocardial infarction in an adult population.

Objective

We examined the benefits of bone marrow‐derived progenitor cells treatment modality for the pediatric patient.

Methods and Results

We present our first case of transcoronary autologous stem cell transplantation in a 9‐year‐old girl with refractory congestive heart failure secondary to myocardial infarction 1 year after transcatheter revascularization. The child received daily injections of granulocyte colony‐stimulating factor for 3 days prior to the bone marrow aspiration. The bone marrow cells were isolated to constitute CD133 + /CD34 + more than 90% of the total number. Subsequently, the progenitor cell suspension was injected via a transcoronary catheter without any complication. Three months after stem cell therapy, her cardiac function, assessed by both cardiac magnetic resonance and echocardiogram, has been improved with the left ventricular ejection fraction at 47% compared to the baseline of 30%.

Conclusion

This is the first reported pediatric case of successful transcoronary injection of bone marrow‐derived progenitor cells for end‐stage heart disease. The procedure is considered safe and feasible for the pediatric population. Copyright © 2010 Wiley Periodicals, Inc.     

Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study.

OBJECTIVES: Stem cell therapy may be useful in chronic myocardial infarction (MI); this is conceivable, but not yet demonstrated in humans. BACKGROUND: After acute MI, bone marrow-derived cells improve cardiac function. METHODS: We treated 18 consecutive patients with chronic MI (5 months to 8.5 years old) by the intracoronary transplantation of autologous bone marrow mononuclear cells and compared them with a representative control group without cell therapy. RESULTS: After three months, in the transplantation group, infarct size was reduced by 30% and global left ventricular ejection fraction (+15%) and infarction wall movement velocity (+57%) increased significantly, whereas in the control group no significant changes were observed in infarct size, left ventricular ejection fraction, or wall movement velocity of infarcted area. Percutaneous transluminal coronary angioplasty alone had no effect on left ventricular function. After bone marrow cell transplantation, there was an improvement of maximum oxygen uptake (VO2max, +11%) and of regional 18F-fluor-desoxy-glucose uptake into infarct tissue (+15%). CONCLUSIONS: These results demonstrate that functional and metabolic regeneration of infarcted and chronically avital tissue can be realized in humans by bone marrow mononuclear cell transplantation.     

骨髓干细胞移植与冠状动脉腔内支架置入术治疗冠心病疗效对比

目的对比观察经皮腔冠状动脉内自体骨髓间充质干细胞(BMMSCs)移植与支架置入术治疗冠心病并心力衰竭的效果。方法自体骨髓干细胞移植组(干细胞组)26例,将备好的自体BMMSCs悬液经心导管自冠状动脉注入缺血或梗死区及其周围心肌;支架置术入组(支架组)30例,经皮腔冠状动脉内置入支架。对比观察2组治疗后3个月患者症状改善、心脏形态和功能变化。结果2组治疗后均无死亡,无低心排综合征、新的心肌缺血及恶性心律失常;2组治疗3个月后,心绞痛发作次数较治疗前均明显减少(P<0.01),心功能提高Ⅰ~Ⅱ级,生活质量明显改善;与治疗前相比,治疗后3个月左心室收缩末直径均缩短(P<0.05),心脏收缩速度(干细胞组P<0.01,支架组P<0.05)、射血分数(干细胞组P<0.01,支架组P<0.05)及心排血量(P<0.01)均明显提高;2组间对比差异无统计学意义(P>0.05)。结论经皮冠状动脉内途径自体BMMSCs治疗冠心病并心力衰竭是安全、有效、可行的;它与冠状动脉内支架置入术相比,近期疗效无差异。     

自体骨髓单个核细胞移植治疗冠心病心力衰竭的临床研究

目的:评价经冠状动脉内注射自体骨髓单个核细胞治疗冠心病心力衰竭患者的有效性。方法:82例冠心病心力衰竭患者随机入选本项前瞻性、对照试验(其中49例患者为细胞移植组,33例为常规治疗组)。2组患者均接受标准药物治疗,细胞移植组49例患者同时接受自体骨髓单个核细胞移植。1年后随访临床情况及超声心动图、单光子放射计算机断层显像术和血浆脑钠肽测定结果,比较2组治疗前后心功能指标和心肌灌注缺损区面积。结果:细胞移植组与常规治疗组比较,左室射血分数增加,心肌灌注缺损面积降低,血浆脑钠肽下降,差异均有统计学意义(P<0.05)。结论:经皮冠状动脉内移植骨髓单个核细胞治疗冠心病心力衰竭,能有效改善左室收缩功能和心肌灌注。     

First experience with the use of bone marrow stem cells for regeneration therapy of ischemic heart disease.

AIM: To elucidate feasibility of the use of autologous bone marrow stem cells in candidates to myocardial revascularization- patients with ischemic heart disease and cardiosclerosis after myocardial infarction. METHODS: Between January 2003 and January 2004 25 men aged 56.3+/-5.4 years with ischemic heart disease were subjected to cell therapy including 4 patients with heart failure and 5 - with acute coronary syndrome. Subgroup of patients with postinfarction cardiosclerosis consisted of 16 men satisfying the following criteria: (1) history of myocardial infarction with scar formation; (2) class III-IV angina; (3) presence of indications for endovascular or surgical intervention on coronary arteries. Study protocol included clinical examination, coronary angiography; dobutamine stress-, contrast- and tissue echocardiography with assessment of segmental myocardial perfusion, systolic and diastolic left ventricular function. RESULTS: There were no complications during bone marrow sampling and administration of cells. All patients were restudied 1 month after transplantation. Improvement of clinical state without complications and adverse effects of the procedure noted in all patients was associated with lowering of mean angina class (from 3.4 to 1.4, p<0.05); decrease of NYHA heart failure class (from 3.1 to 1.5); rise of left ventricular ejection fraction (from 42.9 to 56.3%); decrease of average number of asynergic segments (from 5.3+/-0.7 to 2.1+/-0.3, p<0.01). Systolic velocity before intervention was 2.3 cm/s, after procedure in segments subjected to isolated revascularization it increased up to 4.8 cm/s, while in those subjected to revascularization combined with administration of stem cells - up to 6.2 cm/s. Contrast echocardiography in 9 patients demonstrated augmented myocardial perfusion in regions exposed to cell therapy. CONCLUSION: Transplantation of autologous bone marrow stem cells to ischemic heart disease patients - candidates for myocardial reperfusion - turned out to be safe and well tolerated procedure. Combination of myocardial revascularization with administration of stem cells into regions of postinfarction scars was associated with improvement of total and local myocardial contractility and normalization of left ventricular diastolic filling. Cell therapy facilitated augmentation of myocardial perfusion.     

经冠状动脉自体骨髓单个核细胞移植治疗急性心肌梗死的安全性观察

目的采用随机对照研究方法观察经冠状动脉自体骨髓单个核细胞(BM-MNCs)移植治疗急性心肌梗死(AMI)的安全性。方法入选184例AMI患者,分为细胞移植组92例和对照组92例,两组患者在药物治疗基础上,分别在介入治疗同时,经微导管于梗死相关动脉内支架远端注入自体BM-MNCs悬液或等量的肝素生理盐水(对照组)。记录骨髓收集及分离过程中可能出现的迷走反射(如面色苍白、晕厥、恶心、低血压甚至休克)、心绞痛发作、心力衰竭加重等,细胞悬液输注中可能出现的心律失常(窦性心动过缓、窦性停搏或三度房室传导阻滞、心室颤动)、低血压、栓塞等不良反应。监测术后1周内体温、心率、血压、心肌酶谱变化,并根据预先设定的时间点行24小时动态心电图、血常规、肝肾功能、血糖、血脂、血尿酸、心肌酶谱和高敏C反应蛋白(hs-CRP)检测,定期复查冠状动脉造影和经胸超声心动图。计划随访2年,记录主要心脏事件发生率、支架内再狭窄以及肿瘤等发生情况。结果在骨髓收集和分离过程中患者未出现心绞痛发作、心力衰竭加重等并发症,迷走反射相关不良反应均为一过性。两组患者平均随访(14．5±8．1)个月。与对照组相比,移植组围手术期及随访期间不良事件发生率差异无统计学意义:围手术期(≤1周)4．3％比5．7％(P>0．05);术后3个月为3．5％比2．4％(P>0．05);术后6个月至30个月为11．7％比14．3％(P>0．05)。未发现与移植相关的恶性心律失常、感染、心肌缺血加重、支架内再狭窄增加等。随访期间未发生死亡、新发肿瘤、栓塞等事件。同时,与对照组相比,BM-MNCs移植可以在介入治疗的基础上进一步提高左室射血分数。结论经冠状动脉自体BM-MNCs移植治疗AMI安全可行,且能改善心功能。     

骨髓细胞移植对不同程度衰竭心脏功能恢复的研究

目的探讨骨髓干细胞移植(BMT)对哪种程度的心力衰竭更有效。方法结扎小型猪不同部位左前降支血管,造成不同程度心功能(左心室射血分数,LVEF)变化,2周后,将30只造模型成功动物随机分为3组,高LVEF(HLVEF,LVEF≥50%)组,中LVEF(MLVEF,50%>LVEF≥40%)组,低LVEF(LLVEF,LVEF<40%)组,每组分为两个亚组,各组随机经冠状动脉内移植骨髓单个核细胞或磷酸盐缓冲液(PBS),每组各5只动物。结果移植后4周,注射PBS动物LVEF呈进行性下降;而MLVEF+BMT组较移植前增加11.9%(P<0.05),明显高于HLVEF+BMT组和LLVEF+BMT组。冠状动脉造影显示,只有MLVEF+BMT组侧支循环数量较移植前有显著性增加。免疫组织化学显示,注射BMT的3组血管密度明显高于注射PBS的3组,以MLVEF+BMT组最明显。结论经冠状动脉内自体BMT更有利于中度心力衰竭受体心脏功能恢复和血流灌注改善。     

自体骨髓单个核细胞移植对8例异常Q波扩张型心肌病患者心功能的影响

目的研究自体骨髓单个核细胞(ABMMNCs)经冠状动脉移植对伴有异常Q波的扩张型心肌病(DCM)患者心功能的影响。方法选择2005年6月至2006年5月在哈尔滨医科大学附属第二临床医学院心内科住院的8例体表心电图伴有异常Q波的原发性DCM患者,在常规抗心衰药物治疗的同时,进行冠状动脉造影并进行ABMMNCs移植;在术前和术后3个月、6个月分别行体表心电图及超声心动图检查。结果术后3个月和6个月,8例患者左室射血分数(LVEF)、左室舒张末期内径(LVDd)、左室收缩末期内径(LVSd)虽然较术前有所改善,但差异无显著性意义(P>0.05)。患者术后心电图仍存在异常Q波,与术前无差异。结论经冠状动脉移植ABMMNCs,未证明能改善伴有Q波的DCM患者的心功能。     

Prognostic value of C-reactive protein and neopterin in autologous bone marrow cells transplantation

Relationship between levels of C-reactive protein (CRP) and neopterin and changes of left ventricular function was studied in 23 patients with heart failure (mean age 48.5+/-11.5 years) subjected to transplantation of autologous bone marrow cells (TABMC). Cells were administered intracoronary irrespective of coronary revascularization (in 11 patients) or during angioplasty (in 5 patients), intracoronary or intra-cardially during aorto coronary bypass surgery (in 7 patients). Reverse correlation was observed between left ventricular ejection fraction (EF) and stroke volume (SV) and blood plasma levels of CRP and neopterin. Efficacy of functional regeneration of the myocardium assessed 1 month after TABMC was related to blood plasma levels of CRP and neopterin before treatment. In all patients with normal initial levels of markers of inflammation EF and SV rose. Among patients with initially elevated levels of CRP and neopterin more positive changes of EF and SV occurred in those subjects in whom lowering of inflammation markers took place during 1 month after TABMC.     

自体骨髓单个核细胞移植治疗扩张型心肌病的临床研究

目的研究自体骨髓单个核细胞(ABMMNCs)经冠状动脉(冠脉)移植对扩张型心肌病(DCM)患者心功能的影响及其安全性。方法16例扩张型心肌病患者,按患者的意愿分成两组移植组(n=10)在药物治疗的同时,通过冠脉转运将ABMMNCs移植入心肌组织内;对照组(n=6)只进行相关的药物治疗;两组在术前和术后6个月分别行超声心动图及动态心电图检查。结果超声心动图检查显示移植组的左心室射血分数(LVEF)较术前明显增高,左心室舒张末期内径(LVDd)、左心室收缩末期内径(LVSd)较术前明显降低,左心房内径(LAD)也较术前明显降低。而对照组的LVEF,LVDd及LVSd虽然较6个月前有所改善,但差异无统计学意义(P>0.05)。术中及术后随访6~12个月均无恶性心律失常和其他合并症发生。结论ABMMNCs经冠脉移植,可以治疗扩张型心肌病,改善心脏功能,而且较为安全。     

骨髓间质干细胞移植对心力衰竭大鼠心室重构影响的实验研究

目的 研究骨髓间质干细胞移植对异丙基肾上腺素致心力衰竭(心衰)大鼠心脏功能及心室重构的影响,进而探讨细胞移植影响心脏功能的可能机制.方法 雄性Wistar大鼠60只,取其中的10只作为假手术组,单纯开胸.另外50只皮下注射异丙基肾上腺素(170 mg/kg)连续4 d,建立大鼠心衰模型.末次给药后4周,将左心室射血分数<70%的大鼠(共26只)随机分成2组:移植组(n=13)和对照组(n=13),前者心肌内注射来源于雄性Wistar幼鼠的骨髓问质干细胞悬液(2 ×107/ml,150μl),后者心肌内注射等量的细胞培养液.移植前和移植后4周,多普勒超声心动仪测定大鼠心脏功能、HE及Masson's染色评估心肌病理学改变、荧光显微镜观察移植细胞、RT-PCR和Western blot检测各组心肌组织中Ⅰ、Ⅲ型胶原、基质金属蛋白酶(MMP)-2,9的表达.结果 心衰大鼠心肌组织发生了弥漫性纤维化.移植组左心室射血分数及短轴缩短率明显高于对照组[(78.51±6.78)%比(65.40±12.33)%,(42.09±6.53)%比(32.38±10.22)%,P均<0.05],左心室收缩末径明显小于对照组[(2.91±0.54)mm比(3.83±0.69)mm,P<0.05].移植组心肌组织内可以观察到移植细胞的存在,心脏纤维化面积明显小于对照组(P<0.05),心肌组织内Ⅰ、Ⅲ型胶原,MMP-2、MMP-9的表达下调.结论 骨髓间质干细胞移植通过影响心室重构相关因子进而改善发生了弥漫性纤维化的心衰大鼠的心脏功能.     

COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133<Superscript>+</Superscript> Bone Marrow Stem Cells to Placebo in Patients After Acute Myocardial Infarction and Left Ventricular Dysfunction: Study Rationale and Design

Stem cell therapy has emerged as a promising approach to improve healing of the infarcted myocardium, to treat or prevent cardiac failure, and to restore lost cardiac function. Despite initial excitement, recent clinical trials using nonhomogenous human stem cells preparations showed variable results, raising concerns about the best cell type to transplant. Selected CD133⁺ hematopoietic stem cells are promising candidate cells with great potential. COMPARE-acute myocardial infarction (AMI) study is a phase II, randomized, double-blind, placebo-controlled trial evaluating the safety and effectiveness of intracoronary CD133⁺-enriched hematopoietic bone marrow stem cells in patients with acute myocardial infarction and persistent left ventricular dysfunction. Patients who underwent successful percutaneous coronary intervention and present a persistent left ventricular ejection fraction <50% will be eligible to have bone marrow aspiration and randomized for intracoronary injection of selected CD 133⁺ bone marrow cells vs placebo. The primary end point is a composite of a safety and efficacy end points evaluating the change at 4 months in the coronary atherosclerotic burden progression proximal and distal to the coronary stent in the infarct related artery; and the change in global left ventricular ejection fraction at 4 months relative to baseline as measured by magnetic resonance imaging. The secondary end point will be the occurrence of a major adverse cardiac event. To date, 14 patients were successfully randomized and treated without any protocol-related complication. COMPARE-AMI trial will help identify the effect of a selected population of the bone marrow stem cells on cardiac recovery of infarcted myocardium.     

Combined percutaneous revascularization and cell therapy after failed repair of anomalous origin of left coronary artery from pulmonary artery

This report shows the course of an infant with an abnormal left coronary artery origin arising from the pulmonary artery who underwent failed surgical reimplantation. Treatment entailed combined stent revascularization followed by intracoronary infusion of bone marrow‐derived mononuclear cells. The patient was admitted with an acute coronary syndrome and low cardiac output; he was endotracheally intubated under respiratory assistance. Fourteen months after intracoronary infusion of autologous bone marrow‐derived mononuclear cells, the infant remains symptom‐free with significant recovery of the left ventricular function. These findings suggest that the combination of percutaneous revascularization and cell therapy should be considered in those infants or children in whom salvage therapy for ischemic heart disease is required. © 2009 Wiley‐Liss, Inc.     

经冠状动脉注射骨髓单个核细胞影响心肌细胞凋亡的实验研究

目的观察经冠状动脉注射方式移植骨髓单个核细胞对心脏功能的改善和心肌细胞凋亡的影响。方法结扎小型猪冠状动脉制备心肌梗死模型，然后经冠状动脉注射骨髓单个核细胞，术后3周用超声心动图以及左心室造影检测心功能．核素心肌显像观察心肌灌注，冠状动脉造影观察侧支循环形成．用TUNEL检测心肌细胞凋亡。结果把骨髓单个核细胞通过冠状动脉注射到猪心肌梗死模型，显示左心室dp／dtmax较对照组增高，心肌灌注显著改善。冠状动脉有侧支循环形成，缺血心肌细胞；较对照组减少了53．6％结论骨髓单个核细胞心肌内移植可改善心脏收缩功能，可能与移植细胞抑制心肌细胞凋亡有关。     

Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure the Danish stem cell study--congestive heart failure trial (DanCell-CHF)

BACKGROUND: It has been suggested that myocardial regeneration may be achieved by a single intracoronary bone marrow derived stem cell infusion in selected patients with ischaemic heart disease. The effect is uncertain in patients with chronic ischaemic heart failure and it is not known whether repeated infusions would have additional positive effects. AIMS: To assess whether two treatments of intracoronary infusion of bone marrow stem cells, administered 4 months apart, could improve left ventricular (LV) systolic function in patients with chronic ischaemic heart failure. METHODS: The study was prospective and non-randomised, comprising an observational baseline period of 4 months followed by an interventional period of 12 months. Intracoronary bone marrow cell infusion was performed at the end of the baseline period and repeated 4 months later. RESULTS: 32 patients were included. LV ejection fraction remained unchanged (33+/-9% vs. 34+/-10% after 8 months, p=0.30). Likewise, there was no significant change in LV end-systolic volume, wall motion score index (WMSI) or contractile reserve. At 12 months, a decrease in target vessel WMSI was seen (2.17+/-0.34 vs. 2.06+/-0.46, p=0.02). Furthermore, NYHA class improved (p<0.0001). No deaths were observed. CONCLUSION: In this non-randomised study, no change in LV ejection fraction could be demonstrated after repeated intracoronary bone marrow stem cell treatment in patients with chronic ischaemic heart failure.     

自体骨髓单个核细胞可安全治疗前壁心肌梗死后心力衰竭

目的 评价经冠状动脉内注射自体骨髓单个核细胞治疗前壁心肌梗死后心力衰竭的安全性.方法 15例前壁心肌梗死患者接受经皮冠状动脉介入治疗(PCI)和药物治疗同时,进行冠状动脉内自体骨髓单个核细胞移植.细胞治疗前后测定血浆及骨髓中CD34+细胞含量;移植前、移植后24 h和随访12个月时分别测定血浆红细胞(RBC)、血红蛋白(Hb)、网织红细胞、D-二聚体(D-Dimer)、N末端B型钠尿肽原(NT-proBNP)、超敏C反应蛋白(high sensitive-C reactive protein,hs-CRP)、肌钙蛋白T(troponin T,TnT)、心肌型肌酸激酶同工酶(CK-MB)、尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)及尿酸(uric acid,UA)水平.入组及随访12个月时行动态心电图(Holter)评价心律失常发生情况,观察并记录移植前后及随访过程中发生的不良反应.结果 分离后骨髓单个核细胞数量为(1.48±0.52)×109;CD34+细胞占1.28%±0.17%,数量为(18.57±9.14)×106.移植前循环血中CD34+细胞0.33%±0.12%,术后24 h达峰值1.30%±0.35%,72 h基本恢复至移植前水平0.53%±0.21%.移植后24 h血浆NT-proBNP较移植前无显著性变化(1 864.00±412.60μg/L比1 864.00±369.70μg/L,P0.05),随访12个月时较基线显著降低(701.05±154.60μg/L比1 864.00±369.70μg/L,P<0.05).移植后2、6、14、24 h血浆TnT、CK-MB水平较移植前均无显著变化.与基线相比,移植后24 h、12个月血浆BBC、Hb、网织红细胞、D-Dimer、hs-CRP及肝、肾功能均无显著变化.术后12个月随访未见恶性心律失常发生.结论 经冠状动脉注射骨髓单个核细胞未引起微栓塞、炎症反应及心肌损伤,不诱发或加重心力衰竭,对血液系统、肝、肾功能及凝血功能无影响,长期随访未见与移植相关的严重不良反应.本研究提示经冠状动脉注射自体骨髓单个核细胞治疗方法是安全、可行的.