Intramyocardial bone marrow cell transplantation and the progression of coronary atherosclerosis in patients with chronic myocardial ischemia

BACKGROUND: Cell therapy has been proposed as a novel treatment strategy for patients with ischemic heart disease. However, two recent studies suggested that cardiac cell transplantation might aggravate coronary atherosclerosis. The aim of the current study was to assess whether intramyocardial bone marrow cell transplantation in patients with chronic myocardial ischemia is associated with progression of coronary atherosclerosis. METHODS: In 30 patients with chronic ischemia, bone marrow was aspirated from the iliac crest. During mononuclear cell isolation, coronary angiography was performed. Thereafter, 94+/-18 x 10(6) cells were injected intramyocardially (NOGA system) in regions with ischemia on technetium-99m tetrofosmin SPECT. RESULTS: During the 12-month follow-up period, there was no clinical evidence of progression of atherosclerosis. CCS class improved from 3.4+/-0.5 to 2.4+/-0.8 at 3 months, 2.4+/-0.9 at 6 months and 2.5+/-0.9 at 12 months (P<0.01). MRI-determined left ventricular ejection fraction increased from 51+/-12% to 54+/-12% at 3 months (P<0.01) and the number of ischemic segments per patient on SPECT decreased from 5.2+/-2.6 to 2.1+/-2.2 at 3 months (P<0.01). Repeat coronary angiography at 4 months revealed that bone marrow cell transplantation did not decrease minimal luminal diameter (1.81+/-0.80 mm versus 1.79+/-0.82 mm, P = NS) or mean luminal diameter (2.48+/-0.85 mm versus 2.46+/-0.86 mm, P = NS). Similarly, the percentage diameter stenosis (32+/-19% versus 32+/-20%, P = NS) and the atheromatosis severity score (4.78+/-2.40 versus 4.80+/-2.40, P = NS) remained unchanged. CONCLUSION: Intramyocardial bone marrow cell transplantation in patients with chronic myocardial ischemia was not associated with significant progression of atherosclerosis.     

Predictors of response to intramyocardial bone marrow cell treatment in patients with refractory angina and chronic myocardial ischemia

Background

We previously showed that intramyocardial bone marrow cell (BMC) injection in patients with refractory angina and chronic myocardial ischemia improves myocardial perfusion, cardiac function and disease-related complaints. Treatment effect varied between patients, but the predictors of response remain to be identified. Therefore, the aim of the present study was to assess whether patient characteristics, procedural data and baseline measurements influence the response to intramyocardial BMC treatment in a large cohort of refractory angina patients.

Methods and results

In 120 patients (64 ± 9 years, 88% men) with refractory angina, 97 ± 13 × 10⁶ BMCs were injected intramyocardially in regions with stress-inducible ischemia as assessed by single photon emission computed tomography (SPECT). Canadian Cardiovascular Society angina (CCS) class, quality-of-life score, exercise testing, SPECT and magnetic resonance imaging were performed at baseline and at 3 months follow-up demonstrating significant improvements in CCS class, quality-of-life, exercise capacity, myocardial perfusion and left ventricular function (all variables P < 0.001). Multivariate analysis was performed to evaluate the influence of patient characteristics, procedural data and baseline measurements on BMC treatment response. Based on the improvement of myocardial perfusion at stress, diabetes and a large number of ischemic segments at baseline were shown to be independently associated with a large response to BMC therapy.

Conclusion

The present study demonstrates that diabetes and a large number of ischemic segments are predictors of a large response to intramyocardial BMC injection in refractory angina and chronic ischemia. Furthermore, the safety and efficacy results of previous trials are now confirmed in a larger study population.     

骨髓间充质干细胞移植治疗心肌梗死的研究进展

溶栓、经皮冠状动脉介入治疗及常规药物治疗可挽救许多急性心肌梗死患者的生命,但不能从根本上恢复心肌细胞数量。骨髓间充质干细胞(BM-MSCS)是骨髓中一种具有多向分化潜能的细胞,可被诱导分化为心肌样细胞,改善梗死区的血液供应及心肌重构,为心肌梗死的治疗带来了新的希望。本文就BM-MSCS移植治疗心肌梗死的方式,移植的时机及临床应用等方面作一综述。     

Intramyocardial autologous bone marrow cell transplantation for ischemic heart disease: A systematic review and meta-analysis of randomized controlled trials

Objective

This study was undertaken to evaluate the efficacy of intramyocardial bone marrow cell (BMC) transplant therapy for ischemic heart disease (IHD).

Methods

The PubMed, Embase, and Cochrane Library databases through October 2013 were searched for randomized clinical trials (RCTs) of intramyocardial BMCs to treat IHD. The primary endpoint was change in left ventricular ejection fraction (LVEF). Secondary endpoints were changes in left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV). Weighted mean differences for the changes were estimated with a random-effects model.

Results

Eleven RCTs with 492 participants were included. Intramyocardial BMC transplantation increased LVEF (4.91%; 95% confidence interval [CI] 2.84%–6.99%; P < 0.00001), reduced LVESV (10.66 mL; 95% CI, −18.92 mL to −2.41 mL; P = 0.01), and showed a trend toward decreased LVEDV (−7.82 mL; 95% CI, −16.36 mL–0.71 mL; P = 0.07). Patients suitable for revascularization with coronary artery bypass grafting had greater improvement in LVEF (7.60%; 95% CI, 4.74%–10.46%, P < 0.00001) than those unsuitable for revascularization (3.76%; 95% CI, 2.20%–5.32%; P < 0.00001). LVEDV reduction was also more significant in revascularizable IHD (−16.51 mL; 95% CI, −22.05 mL to −10.07 mL; P < 0.00001) than non-revascularizable IHD (−0.89 mL; 95% CI, −8.44 mL–6.66 mL; P = 0.82).

Conclusion

Intramyocardial BMC injection contributes to improvement in left ventricular dysfunction and reduction in left ventricular volume. Patients with revascularizable IHD may benefit more from this therapy.     

Autologous transplantation of bone marrow mononuclear cells for limb ischemia in a caucasian population with atherosclerosis obliterans

Background. Autologous transplantation of bone marrow mononuclear cells (ATBMMNC) has been used successfully in critical limb ischemia. All reported patients were of Asian descent, however, and several studies included only young patients with thromboangiitis obliterans. Whether the beneficial results can be extrapolated to older Caucasian patients with atherosclerosis obliterans and a heavy burden of cardiovascular risk factors remains unclear. Methods. We enrolled 16 patients (age 78 ± 2 year) with critical limb ischemia and a high prevalence of hypertension, smoking, diabetes, hypercholesterolemia and uremia. Mononuclear cells were isolated from the bone marrow and injected in the gastrocnemius muscle of the affected limb. Results. Four patients died because of progressive gangrene (two) or unrelated causes (two). Three patients required an amputation and one patient a femorocrural bypass within 12 weeks. The remaining eight patients had a modest improvement of resting pain and/or trophic lesions. Transcutaneous oxygen pressure (ratio lesion/reference) improved from 0.51 ± 0.11 before to 0.86 ± 0.03 (P < 0.001) after 12 weeks, whereas ankle‐brachial index did not change significantly (0.42 ± 0.15 vs. 0.59 ± 0.1; P = 0.23). The number of visible collateral vessels on digital subtraction angiography changed with 0.89 ± 0.86 on a scale of 1–4 (P = 0.33). Capillary surface area in a biopsy of gastrocnemius, evaluated by immunostaining for endothelial nitric oxide synthase, increased from 0.61 ± 0.07% to 2.38 ± 0.73% (P < 0.05). Conclusions. Although ATBMMNC was associated with objective signs of neovascularization, symptomatic improvement was only modest and restricted to the least affected patients. The discrepancy with previous findings may be related to the high prevalence of cardiovascular risk factors which causes endothelial progenitor cell dysfunction.     

Autologous intracoronary mononuclear bone marrow cell transplantation in chronic ischemic cardiomyopathy in humans

BACKGROUND: Recent data suggest that transplantation of autologous bone marrow cells (BMC) may contribute to myocardial repair after acute myocardial infarction. We hypothesized that patients with chronic ischemic cardiomyopathy could also benefit from autologous BMC transplantation in addition to established heart failure therapy. METHODS AND RESULTS: Five patients with chronic ischemic cardiomyopathy caused by anterior myocardial infarction, 1.3+/-0.5 years ago and open infarct artery, received autologous mononuclear BMC transplantation via balloon catheter in the target vessel at the site of previous occlusion. Patients were followed up at 3 months (left heart catheterisation, 2D-echocardiography, dobutamine stress echocardiography, cardiopulmonary exercise testing) and at 12 months (2D-echocardiography, cardiopulmonary exercise testing). Follow-up examination showed no significant improvement neither in global, regional, and microvascular function, nor in physical performance. CONCLUSIONS: In this pilot trial intracoronary transplantation of autologous, mononuclear BMC did not lead to any significant improvement in myocardial function and physical performance of patients with chronic ischemic heart disease.     

陈旧性前壁心肌梗死患者自体骨髓单个核细胞移植后左室心肌灌注及收缩功能的变化

目的　评价经冠状动脉内自体骨髓单个核细胞移植对陈旧性心肌梗死患者心功能和心肌灌注的影响及其安全性。方法与结果　入选 10例陈旧性前壁心肌梗死患者 ,在冠状动脉造影和介入治疗后 ,经冠状动脉内灌注导管将自体骨髓单个核细胞缓慢注入前降支。随访 3个月后 ,左室射血分数由术前 4 5 3%± 9 8%升高至 5 4 5 %± 6 5 % (P =0 0 0 3) ;2 0 1 Tl心肌灌注显像 (SPECT)显示左心室心肌灌注明显改善 ,即刻和延迟心肌灌注评分分别由术前的 2 9 5± 5 8和 2 8 6± 6 3降低至 2 3 9±5 7和 2 3 0± 6 1(P均 <0 0 1) ,没有手术有关的并发症和恶性心律失常发生。结论　陈旧性前壁心肌梗死患者经冠状动脉内自体骨髓单个核细胞移植 ,可显著改善左室收缩功能和心肌灌注 ,并且具有良好的临床操作安全性。     

Safety of intramyocardial injection of autologous bone marrow cells to treat myocardial ischemia in pigs

OBJECTIVE: The purpose of this study is to determine the potential adverse consequences of intracardiac injections of bone marrow mononuclear cells (BMCs) to facilitate the revascularization of ischemic myocardium. BACKGROUND: Bone marrow mononuclear cells are used to treat heart failure, though there are few studies that evaluated the safety of BMC transplantation for chronic myocardial ischemia. METHODS: The pigs received coronary ameroid constrictors to induce chronic myocardial ischemia and left ventricular dysfunction. At 4 weeks, autologous BMCs were injected intramyocardially by Boston Scientific Stiletto catheter with low-dose (10(7) cells) or high-dose BMC (10(8)). Control animals received saline. Blood samples were collected for hematological and chemical indices, including cardiac enzyme levels at regular time intervals postinfarction. At 7 weeks, animals underwent electrophysiological study to evaluate the arrhythmic potential of transplanted BMC, followed by necropsy and histopathology. RESULTS: No mortalities were associated with intramyocardial delivery of BMC or saline. At Day 0, the total creatine phosphokinase (CPK) was in the normal range in all groups. All groups had significant elevations in CPK after ameroid placement, with no significant differences between groups. At 7 weeks, CPK in all groups had returned to pretreatment levels. Electrophysiological assessment revealed that one control animal had an inducible arrhythmia. No arrhythmias were induced in low- or high-dose BMC-treated pigs. There were no histopathological changes associated with BMC injection. CONCLUSION: This study showed, in a clinically relevant large-animal model, that catheter-based intramyocardial injection of autologous BMC into ischemic myocardium is safe.     

经冠状动脉自体骨髓干细胞移植治疗急性前壁心肌梗死的临床研究

目的 评价经冠状动脉自体骨髓干细胞（MSCs）移植治疗急性前壁心肌梗死的有效性和安全性.方法 入选我院心内科急性前壁心肌梗死住院患者20例,随机分成两组,每组10例.治疗组PCI后经冠状动脉行骨髓干细胞移植,对照组单纯PCI治疗.出院前及移植后定期复查心脏彩超、心肌核素显像（SPECT）及6 min步行试验.结果 ①心脏彩超检查：治疗组术后心功能逐渐好转,随访6个月左室射血分数（LVEF）由（50.5±6.6）%提高至（63.9±7.9）%（P＜0.05）,与对照组比较,差异有统计学意义（P＜0.05）.②SPECT：对照组无明显变化,治疗组心肌灌注显像明显改善.③6 min步行试验：随访6个月,两组较出院前均明显改善（P＜0.05）,组间比较差异无统计学意义（P＞0.05）.结论 经冠状动脉自体MSCs移植治疗急性前壁心肌梗死安全、有效,可能与MSCs再生心肌、抑制心室重构、改善心功能有关.     

经冠状动脉自体骨髓单个核细胞移植治疗缺血性心力衰竭

目的观察经冠状动脉自体骨髓单个核细胞(mononuclearbonemarrowcell,MBMC)移植治疗缺血性心力衰竭(IHF)的可行性、效果、安全性及不良反应。方法2002年12月至2004年3月,41例缺血性心力衰竭患者入选此前瞻性研究,分为两组。(1)细胞移植组:14例经梗死相关冠状动脉超选择性移植,于气囊充盈下高压注入2mLMBMC(2×106/mL),重复注入6～8次,平均共计(3.28±0.44)×107MBMC;13例经冠状动脉选择性移植,气囊未充盈下高压注入移植细胞,细胞数与上相同。(2)对照常规治疗组:共14例,除细胞移植外其他治疗均相同。结果27例细胞移植患者手术均安全,2例于细胞注入后15～30min感发冷,30min后好转;2例细胞注入时出现短暂自限性室性早搏,术后48h持续心电监测未出现新的心律失常;随访3个月时,细胞移植组心力衰竭症状明显好转,射血分数(EF)和心搏量(SV)增加,左心室收缩末期容积(LVESV)减少,正电子发射体层摄影(PET)心肌代谢显像示代谢活力心肌增加(23.94±7.28)%(P=0.015);术后第3天、第7天脑钠素(BNP)水平较术前明显下降,心钠素(ANP)水平在术后第7天明显上升;随访6个月1例心力衰竭加重再度住院,无一例死亡。对照组心功能恶化,再入院率71.4%,2例死亡。结论自体骨髓单个核细胞经冠状动脉移植修复心肌对改善心功能是安全有效的。     

骨髓干细胞移植对大鼠急性心肌梗死后室性心律失常的影响

目的观察骨髓干细胞移植对大鼠急性心肌梗死(AMI)后室性心律失常的影响。方法30只AMI大鼠随机分为两组,心肌梗死后30min细胞移植组予以骨髓干细胞注射;对照组予以等量无血清培养基注射。观察注射后当天、28天24h动态心电图心律失常情况。结果注射后当天,两组心律失常无差异。注射后28天,细胞移植组1只、对照组4只大鼠死亡,细胞移植组室性心律失常的发生率显著降低。结论骨髓干细胞移植可有效减少AMI后室性心律失常的发生。     

自体骨髓干细胞移植治疗慢性肝衰竭研究

目的探索自体骨髓干细胞移植对肝衰竭患者的治疗作用,为干细胞移植的临床应用研究提供基础。方法35例慢性重症肝病患者,20例行自体骨髓干细胞移植治疗,15例作为对照。在无菌条件下,从患者髂后上棘抽取骨髓30～50ml,分离纯化骨髓干细胞。在局部麻醉下行肝动脉介入,将分离的骨髓干细胞移植于肝脏。患者在移植后1、2、4、8周进行肝功能检测。观察患者移植后不同时间症状改善情况及术后不良反应情况。结果在移植8周后,患者丙氨酸转氨酸逐渐降低,由平均181.7μmolL降至72.1μmolL;总胆红素由平均153.8μmolL降至80.2μmolL;直接胆红素由平均74.1μmolL降至40.5μmolL;白蛋白逐渐升高,由平均26.5μmolL升至31.5μmolL;与对照组相比有明显差异,表明移植后患者肝功能明显改善。干细胞移植后凝血酶原活动度逐渐上升,由术前平均28.2%上升至50.1%。进一步观察自体骨髓干细胞移植对肝衰竭患者生存率的影响,发现移植后1周生存率为100%,4周为95%(1920),8周后为90%(1820),12周后为85%(1720),较对照组生存率明显升高。移植后大多数患者有明显症状改善,移植后8周内腹水减轻10例(50%),食欲改善15例(75%),体力好转11例(55%),腹胀减轻9例(45%)。在20例移植患者中未发现严重并发症,术后有轻度恶心1例,发热1例。结论自体骨髓干细胞移植治疗后,患者肝功能和凝血机制明显改善,生存率提高,症状好转,表明骨髓干细胞移植对肝衰竭患者治疗有效,安全,不良反应少。     

经冠状动脉注入自体骨髓单个核细胞的临床研究

目的评价经冠状动脉内注射自体骨髓单个核细胞治疗心肌梗死患者的有效性。方法共有35例前壁心肌梗死患者人选本项前瞻性、非随机、开放试验（其中20例患者为细胞移植组,15例为对照组）。两组患者均接受标准的介入治疗和药物治疗,细胞移植组的20例患者同时接受自体骨髓单个核细胞移植。两组患者均接受3个月的临床随访及6min步行试验、超声心动图、心肌双核素和心脏核磁等检查。结果3个月的检查结果提示,细胞移植组患者的左室射血分数与常规治疗组相比有显著统计学意义。同时细胞移植组患者的室间隔中段室壁运动位移和左室收缩末容积也有明显改变,细胞移植组显著增加代谢可恢复心肌区占左室的比例。结论经冠状动脉注入自体骨髓单个核细胞可以促进心肌梗死患者寿窜功能恢复和心肌灌沣改善．     

Safety and efficacy of percutaneous intramyocardial bone marrow cell injection for chronic myocardial ischemia: Long‐term results

Background

Intramyocardial injection of bone marrow cells (BMC) in refractory angina patients with chronic myocardial ischemia has shown to be safe and improve clinical status during short‐term follow‐up. However, scarce data are available on long‐term (>12 months) safety and efficacy. Therefore, the occurrence of clinical events and the long‐term clinical effects of intramyocardial BMC injection were evaluated in patients with chronic myocardial ischemia up to 10 years after treatment.

Methods and Results

Patients (n = 100, age 64 ± 9 years, male 88%) with chronic myocardial ischemia who underwent intramyocardial BMC injection between 2004 and 2010 were evaluated. During yearly outpatient clinic visits, the occurrence of clinical events was documented. In addition, clinical status was assessed according to the Canadian Cardiovascular Society (CCS) score and quality of life was measured using the Seattle Angina Questionnaire. These parameters were evaluated at baseline and during the first year, followed by cross‐sectional long‐term follow‐up which was performed in 2011 and 2014. No adverse events considered related to the procedure occurred during 10 years of follow‐up. Observed annual mortality rate and annual myocardial infarction rate were 3.8% and 1.9% per year, respectively. When compared to baseline, CCS class and quality of life remained significantly better during 5‐year follow‐up after BMC treatment (both P < 0.05).

Conclusions

The present long‐term follow‐up study shows that intramyocardial BMC injection in patients with chronic myocardial ischemia is safe and improves both angina complaints and quality of life up to 5 years after BMC treatment.

     

同种异体骨髓基质细胞心肌移植的研究

目的 :研究大鼠同种异体骨髓基质细胞 (BMSCs)移植到心肌梗死区后能否存活 ,并进一步增殖、分化以及对宿主心脏的影响。方法 :结扎大鼠冠状动脉左前降支制作急性心肌梗死模型。 4周后 ,取传两代的体外培养的同种异体BMSCs ,注射到大鼠心肌梗死区 ,为移植组 ;同时设置注射培养基的对照组。移植 4周后检测受体心脏的血流动力学指标 ,然后取标本 ,检测移植细胞存活、分化和组织的血管新生状况。结果 :移植组大鼠心脏血流动力学指标较对照组明显改善 ;同种异体BMSCs移植入心肌梗死区后能够度过急性炎症期 ,而且不引起明显移植排斥反应 ;位于梗死区的移植细胞主要分化为成纤维细胞 ,部分位于心肌梗死区周围的细胞分化为血管内皮细胞 ,并促进了血管新生 ;移植组心肌梗死区及其周围新生血管数目较对照组明显增加。结论 :同种异体BM SCs移植促进心肌梗死后血管新生、改善心功能 ,是用于心肌移植可供选择的种子细胞。     

Tumor cell colonies in bone marrow cultures from patients with small cell carcinoma of the lung

Summary Bone marrow specimens from 27 patients with small cell carcinoma of the lung (17 with limited and 10 with extensive disease) were plated in a culture system that supports the growth of multilineage haemopoietic progenitors CFU-GEMM. In five patients (three with extensive and two limited disease) atypical colonies could be observed that were not identifiable as haemopoietic colonies. Cytological staining and cytochemical examination as well as electronic micrographs suggest that these colonies are derived from metastatic carcinoma cells. The histological examination of marrow cells from three out of these five patients revealed no bone marrow involvement. Additional studies might provide further evidence whether bone marrow cultures are a useful probe in order to monitor bone marrow involvement in patients with small cell carcinoma of the lung.Dedicated to Dr. Werner Lay on his 65th birthday     

自体骨髓单个核细胞移植治疗肝硬化的临床评价

目的探讨肝动脉插管自体骨髓单个核细胞（BM—MNCs）移植治疗肝硬化的安全性、可行性及疗效。方法201例肝硬化患者,其中131例进行自体骨髓单个核细胞移植,70例作为对照组。骨穿采集自体骨髓体外分离纯化骨髓单个核细胞。经肝动脉插管将其移植入肝脏。分别于移植后4、8、12、24周观察血清白蛋白（ALB）、胆碱酯酶（CHE）、凝血酶原活动度（PTA）及总胆红素（TBil）变化情况,观察患者并发症及预后。结果移植组患者移植前血清ALB、CHE及PTA分别为29．33g／L、2387．4U／L和46．4％。移植后4周分别升至32．37g／L、2875．9U／L和53．54％,12周分别为32．95g／L、3190．6U／L和57．24％,24周则分别为32．22g／L、3066．5U／L和56．02％。患者移植后24、周内血清ALB、CHE和PTA水平较治疗前均显著升高,而对照组则无明显升高,两组比较差异有统计学意义。而血清TBil在移植后24周内改善情况与对照组相比差异无统计学意义。两组患者24周内主要并发症发生率及预后情况差异无统计学意义。移植后无严重不良事件发生。结论自体骨髓单个核细胞移植能改善肝硬化患者肝脏合成能力,并有良好的安全性。     

前壁心肌梗死患者自体骨髓单个核细胞移植治疗的可行性研究

目的　评价经冠状动脉内注射自体骨髓单个核细胞治疗心肌梗死患者的可行性。方法　本项前瞻性、非随机、对照研究入选2 2例陈旧性前壁心肌梗死患者(其中1 4例患者为细胞治疗组,8例患者为常规治疗组)。两组患者均接受标准的介入治疗和药物治疗,细胞移植组的1 4例患者采用Over the Wire(OTW )球囊导管将自体骨髓单个核细胞缓慢注入前降支。结果　细胞移植组中1例患者因支架内急性血栓形成而死亡。其余1 3例和常规治疗组的8例患者术中及术后无心肌缺血及心律失常的发生。两组患者均于术后3个月和6个月随访,并行6分钟步行试验、超声心动图、心肌双核素和心脏核磁等检查。3个月的检查结果提示,细胞移植组左室射血分数[( 4 0 .1 2±5 .52 ) %vs( 50 . 37±7. 31 ) % ,P =0 . 0 0 0 1 ],与常规治疗组差异有统计学意义[( 50 .37±7 .31 ) %vs ( 4 4. 0 9±3 .50 ) % ,P =0 . 0 35]。结论　前壁心肌梗死患者经冠状动脉内行自体骨髓单个核细胞移植具有良好的可行性,可以显著改善左室收缩功能。     

Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

AIM: To evaluate the safety and feasibility of bone marrow cell (BMC) transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS: Ten patients (eight males) with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 ml of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS: The median age of the patients was 52 years (range 24-70 years). All patients were discharged 48 h after BMC infusion. Two patients complained ofmild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 (2.19 ± 0.9) and 4 mo (2.10 ± 1.0) after cell transplantation that baseline levels (2.78 ± 1.2). Albumin levels 4 mo after BMC infusion (3.73 ± 0.5) were higher than baseline levels (3.47 ± 0.5). International normalized ratio (INR) decreased from 1.48 (SD = 0.23) to 1.43 (SD = 0.23) one month after cell transplantation. CONCLUSION: BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease.     

骨髓单个核细胞移植和冠状动脉介入治疗后再狭窄关系的实验研究

目的研究骨髓单个核细胞移植对冠状动脉介入治疗后支架内再狭窄的影响。方法用球囊堵闭法制成小型猪急性前壁心肌梗死模型,喂养3周后在左前降支置入支架,同时提取骨髓分离单个核细胞,注入梗死相关血管。饲养4周后做冠状动脉造影定量分析狭窄程度。对支架两端血管组织学切片做苏木精-伊红和天狼猩红染色分析再狭窄原因。结果实验组8头小型猪中有4头发生再狭窄,再狭窄率为50%;对照组9头中有4头发生再狭窄,再狭窄率为44%,两组间比较差异无统计学意义;冠状动脉造影定量分析提示:骨髓单个核细胞治疗组冠状动脉支架内管腔晚期丢失为1·50±1·45mm,对照组为1·31±1·07mm(P=0·736),两组比较差异无统计学意义。结论在小型猪心肌缺血模型中,骨髓单个核干细胞移植不增加冠状动脉介入治疗后支架内再狭窄发生率。