冠心病的干细胞治疗进展

<正> 自2001年Orlic等首次开展干细胞移植治疗冠心病以来,全世界已开展了数十个循证医学研究临床试验,已经有2000多例心肌梗死患者接受了干细胞治疗,为冠心病细胞治疗积累了初步资料。但试验结果不一致。我们重点探讨短期疗效荟萃分析、长期疗效临床试验的最新进展和展望。2007年以来,共有5个骨髓/外周血干细胞移植治疗心肌梗死的临床试验荟萃分析公布。如Abdel-Latif等纳入12个随机对照研究和6个队列研究进行荟萃分析,骨髓单个核细胞(BMCs)移植数量为2×10~5～60×10~9个,随访3～6个月,与对照组比较,左心室射血分数提高3.66%,     

骨髓干细胞动员治疗冠心病

冠心病严重危害着人类的健康。目前的药物、介入治疗和冠脉搭桥术作为治疗冠心病的主要措施,尚未达到理想的目的。细胞治疗作为一种替代手段发挥相当的治疗作用。细胞治疗主要是指将具有分化潜能的自体或异体细胞移植入机体组织,在一定条件下使移植的细胞分化为所需类型的组织细胞,起到修复组织、恢复器官功能的作用。近年来,细胞治疗在冠心病方面的应用是研究的热点。骨髓干细胞动员有可能为冠心病的治疗开辟新的途径。骨髓干细胞是骨髓组织中的一群具有自我更新、多向分化和高度增殖能力的未分化成熟细胞。根据其特性和分化方向可进一步分为骨髓造血干细胞、骨髓内皮祖细胞和骨髓间充质干细胞。骨髓干细胞动员治疗冠心病为一种新的治疗方法,目前主要用于治疗缺心性心肌病,即心肌梗死,不论从其易行性、安全性来说都有着一定的优势。骨髓干细胞动员治疗冠心病的研究非常活跃,尽管如此,其安全性的问题仍存在争议。今后的研究方向应当是研究不同骨髓干细胞方向分化的细胞特征,进行高纯度骨髓干细胞动员,及骨髓干细胞动员的理论研究和实践。     

自体干细胞移植治疗糖尿病足的进展

治疗性血管生成是近年来国内外广泛开展的一项新技术。包括自体骨髓干细胞移植和自体外周血干细胞移植及自体骨髓和外周血干细胞联合移植^[1]。     

自体干细胞移植治疗糖尿病足的进展

治疗性血管生成是近年来国内外广泛开展的一项新技术。包括自体骨髓干细胞移植和自体外周血干细胞移植及自体骨髓和外周血干细胞联合移植^[1]。     

儿童供者外周血造血干细胞采集的临床研究

目的:研究儿童外周血造血干细胞的采集过程以及外周血造血干细胞采集对儿童供者健康的影响,以评估儿童作为异基因造血干细胞移植供者,特别是当干细胞受者为成人时的安全性和有效性。方法:回顾性分析14例儿童作为供者进行外周血造血干细胞的动员、采集过程和采集物的相关临床资料。结果:14例儿童供者中位年龄6(2~10)岁。干细胞采集物用于半相同移植4例,同胞全合移植10例。骨髓联合外周血造血干细胞移植6例,单纯外周血造血干细胞移植8例。供者外周血干细胞采集总次数分别为1次4例,2次5例,3次3例,4次2例。除1例植入失败以外,其他受者均顺利植活。儿童在整个外周血造血干细胞采集过程中无明显不良反应。结论:儿童供者通过分次动员和采集可以采集出足量的造血干细胞用于异基因造血干细胞移植。儿童采集外周血造血干细胞是安全的,儿童供者所采集的外周血造血干细胞能够满足单纯外周血干细胞移植或骨髓联合外周血干细胞移植的需要。     

冠心病的干细胞治疗研究进展

干细胞是一类具有自我复制和多向分化能力的不成熟细胞,已有许多基础和临床研究表明,干细胞有分化为具有收缩功能的心肌细胞、修复受损心肌细胞、增强血管新生等作用,从而缩小心肌梗死面积、改善心功能.我们就干细胞移植治疗冠心病的现状作一综述. 1 干细胞类型 改进现有干细胞功能或筛选新型干细胞是改进细胞类型的两条路径.目前常用于冠心病治疗临床和实验的有以下几种细胞.     

高血压合并冠心病患者PCI后外周血TLR2、TLR4、TNF-α、IL-1β的表达及意义

目的检测高血压合并冠心病患者在经皮冠状动脉介入术(PCI)后外周血中Toll样受体2(TLR2)、Toll样受体4(TLR4)、肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)的表达水平,并探究其临床意义。方法选择2016年3月～2017年8月于孝感市中心医院心血管内科行PCI的50例高血压合并冠心病患者(高血压合并冠心病组)和40例单纯冠心病患者(单纯冠心病组),另选择40例身体健康者作为对照组。冠心病患者按照冠状动脉造影结果,行选择性PCI治疗。在PCI治疗前和治疗后7 d,实时定量PCR(RT-qPCR)检测外周血TLR2和TLR4 mRNA水平,酶联免疫吸附试验(ELISA)检测外周血TNF-α和IL-1β蛋白表达水平。结果 PCI前,高血压合并冠心病组外周血TLR2、TLR4 mRNA水平均显著高于对照组和单纯冠心病组(P0.05);PCI后,高血压合并冠心病组外周血TLR2、TLR4mRNA水平均显著降低(P0.05),但TLR2 mRNA水平仍显著高于对照组(P0.05)。PCI前,高血压合并冠心病组外周血TNF-α、IL-1β蛋白水平均显著高于对照组和单纯冠心病组(P0.05);PCI后,单纯冠心病组、高血压合并冠心病组外周血TNF-α和IL-1β蛋白水平显著降低(P0.05),但仍高于对照组(P0.05)。PCI前后,外周血TLR2、TLR4、TNF-α和IL-1β表达水平均显著呈正相关关系(P0.05)。结论冠心病患者外周血TLR2、TLR4、TNF-α和IL-1β表达量增加,合并高血压可增加其水平,PCI可降低冠心病患者外周血TLR2、TLR4、TNF-α和IL-1β水平。     

脐血干细胞移植治疗心肌梗死的研究进展

干细胞移植为近年来心血管领域研究的热点之一。脐血干细胞在自我更新、增殖分化和体外扩增等方面的潜能，明显优于骨髓干细胞和外周血干细胞，有可能成为未来细胞移植的重要供体。本文对脐血干细胞移植在治疗心肌梗死中进行的基础研究作了简要综述。     

外周血中的内皮细胞与冠心病

外周血的成熟内皮细胞及内皮祖细胞与冠心病具有密切的关系，本文就外周血中成熟内皮细胞及内皮祖细胞数量改变与冠心病发病、治疗和预后等方面研究进展作一综述。     

ABO血型不合同胞间异基因外周血干细胞移植后纯红细胞再生障碍性贫血3例报告

目的：探讨ABO血型不合异基因外周血干细胞移植后纯红细胞再生障碍性贫血(PRCA)的治疗。方法：报道3例病例并进行文献复习。结果：3例HLA配型完全相合、ABO血型主要不合的患者进行同胞间异基因外周血干细胞移植获得成功,但移植后均出现PRCA。1例经大剂量糖皮质激素联合大剂量免疫球蛋白治疗,2例经大剂量糖皮质激素联合血浆置换治疗后血型均转为供者血型,血红蛋白逐渐恢复正常。结论：大剂量糖皮质激素联合血浆置换或大剂量免疫球蛋白是治疗ABO血型不合异基因外周血干细胞移植后PRCA的有效方法。     

CABG联合自体干细胞移植治疗心肌梗死疗效观察

目的观察冠脉搭桥术（CABG）联合经冠状动脉桥血管及心外膜下注入自体外周血干细胞治疗心肌梗死的疗效。方法 32例冠心病心肌梗死患者,随机分为对照组和观察组,各16例。观察组术前5 d使用重组人粒细胞集落刺激因子皮下注射进行外周血干细胞（PBSC）的动员及扩增。CABG术前24 h进行PBSC的采集和浓缩。两组均在非体外循环下行CABG,观察组在完成血管桥吻合后,经桥血管及心外膜下注入PBSC。术前1周及术后3、6个月采用二维超声心动图和99mTc-MIBI心肌灌注显像检测两组患者左心室射血分数（LVEF）、左心室舒张末期内径（LVEDD）及心肌灌注情况。结果术后3、6个月二维超声心动图检查显示两组患者LVEF、LVEDD均较术前改善,组间比较观察组较对照组改善程度更大（P均〈0.05）。术后6个月99mTc-MIBI心肌灌注显像显示两组患者充盈缺损区域均较术前缩小,观察组较对照组充盈缺损区域缩小程度更明显（P均〈0.05）。结论 CABG联合自体外周血干细胞移植治疗心肌梗死安全可行,患者术后心肌灌注和心功能恢复满意。     

急性冠状动脉综合征患者单核细胞核因子-κB活性变化与可溶性细胞间黏附分子-1的关系

目的　观察不同类型冠心病患者外周血单核细胞核因子 κB (NF κB)活性水平变化及其与血浆可溶性细胞间黏附分子 1(sICAM 1)的关系 ,以探讨识别与预测急性冠状动脉综合征 (ACS)的炎性指标。方法　采用夹心酶联免疫吸附法和免疫组织化学染色测定。 6 0例冠心病患者 [30例ACS ,30例稳定性冠心病 (SCHD) ]及 30例对照组的血浆sICAM 1浓度和外周血单核细胞NF κB活性。同时采用直线相关分析法分析NF κB活性与sICAM 1浓度相关性。结果　ACS组NF κB活性和sICAM 1浓度显著高于SCHD组和对照组 (P <0 .0 1) ,而且NF κB活性与sICAM 1浓度呈显著正相关。但SCHD组NF κB活性和sICAM 1浓度与对照组比较 ,差异无显著性意义。结论　ACS组NF κB活性和sICAM 1浓度升高 ,提示其可能与ACS的发生有关 ,血浆sICAM 1浓度水平升高可能是通过NF κB调节途径而实现。     

造血干细胞在心脏中的归巢与分化

利用造血干细胞治疗心脏损伤尤其是由退化、缺血和炎症引起的损伤已被认为是新近发展的重要治疗心脏病变的手段之一。造血干细胞在生理及病理条件下均能归巢于心肌,并能被动员至外周血且参与心脏的自稳态和组织维持。现就造血干细胞在心脏中归巢与分化的机制以及造血干细胞在治疗心脏病变中的应用进行简要综述。     

Circulating progenitor cells in stable coronary heart disease and acute coronary syndromes: relevant reparatory mechanism?

Bone marrow-derived cells which may be involved in cardiac repair/regeneration after ischaemic injury must undergo mobilisation into peripheral blood with subsequent homing and engraftment into the target organ. Mobilisation of the heterogeneous population of stem/progenitor cells in endothelial injury or myocardial ischaemia has been described recently. The number of circulating stem/progenitor cells reflects the endothelial damage, and turnover may be a surrogate marker reflecting the burden of cardiovascular risk factors and prognostic markers in stable coronary heart disease and acute coronary syndromes. Acute coronary syndromes are associated with increased levels of inflammatory and haematopoietic cytokines which, in turn, can mobilise progenitor cells from the bone marrow. Myocardial infarction increases the number of endothelial progenitor cells and other less well-defined subpopulations, such as CD34/c-kit(+) and CD34/CXCR4(+) cells, which may take part in cardiac repair after ischaemic injury. Data on mobilisation of stem/progenitor cells in acute coronary syndromes are summarised here. Cell types, mechanisms of mobilisation, homing and engraftment are discussed and their relevance to clinical outcomes.     

腺病毒转染的肝细胞生长因子对冠心病患者外周造血干细胞的动员作用

目的 探讨经冠状动脉内注射腺病毒（adenovirus,Ad,）转染人肝细胞生长因子（HGF）对严重冠状动脉狭窄患者外周造血干细胞的动员作用。方法 本研究人选18例冠心病患者,分为两组：给药组9例,经冠状动脉注入Ad5-HGF;对照组9例,经冠状动脉注入同等量的生理盐水。所有患者均于冠状动脉造影术前、术后6h、24h及6天抽取外周血,并应用流式细胞仪单克隆荧光抗体标记法检测其外周造血干细胞表面抗原CD34^＋、CD38^＋及CD117^＋。结果 给药组术后6h的CD34^＋明显高于对照组（0,104±0．082比0．022±0．012,P=0．021）,0h、24h及6天的CD34^＋两组之间差异无统计学意义;给药组术后6天的CD117^＋明显高于对照组（0．058±0．058比0．012±0．009,P=0,034）,差异有统计学意义,其余时间点两组间差异均无统计学意义;CD38^＋在各时间点两组间差异均无统计学意义。结论 经冠状动脉内注射转染A5-HGF可能在短时间内引起外周造血干细胞的动员。动员外周造血干细胞可能是HGF参与血管新生和器官组织损伤修复及抗凋亡、改善心功能的一个重要机制。     

血浆内皮功能标志物在心脑血管病中的意义

病理状态下,内皮细胞可被激活、出现功能障碍和受损.内皮功能障碍在心脑血管病的发病过程中起着关键作用,并可通过外周血进行检测.von Willebrand因子浓度能预测冠心病和卒中风险;可溶性血栓调节素浓度与冠心病和卒中的预后相关;可溶性细胞间黏附分子-1能预测颈动脉粥样硬化、冠心病、周围动脉病和糖尿病风险;颈动脉粥样硬化、冠心病和糖尿病患者血浆可溶性E-选择素水平升高;内皮素-1水平升高预示发生充血性心力衰竭的风险增高;注射内皮祖细胞有词望成为治疗心脑血管病的一种新手段.     

心绞痛患者冠状动脉内皮损伤及意义

目的　探讨冠心病患者冠状动脉 (冠脉 )内皮细胞损伤及在冠心病发生、发展过程中的临床意义。方法　 37例心绞痛患者均经冠脉造影证实有明显冠脉狭窄 ,测定其冠状窦和外周血中一氧化氮 (NO)、内皮素 (ET)含量和循环内皮细胞 (CEC)数量 ,比较不稳定性心绞痛、稳定型心绞痛和对照组间相同和不同部位之间指标的差异。结果　不稳定性心绞痛、稳定型心绞痛患者冠状窦和外周血中NO含量较对照组均明显降低 (P <0 0 1或P <0 0 5 ) ,ET含量和CEC数量均明显增高 (P <0 0 1或P <0 0 5 ) ,不稳定性心绞痛组NO含量较稳定型心绞痛组明显降低 (P <0 0 5 ) ,ET含量和CEC数量均明显增高 (P <0 0 1) ,不稳定性心绞痛和稳定型心绞痛患者冠状窦血中NO含量均明显低于外周血 (P <0 0 5 ) ,ET含量和CEC数量均明显高于外周血 (P <0 0 1或P <0 0 5 ) ,对照组冠状窦与外周血相比三项指标均未见明显差别 (P >0 0 5 )。结论　心绞痛患者冠脉局部内皮受损及功能紊乱与病情严重程度相一致 ,内皮损伤的加重可能是病情恶化以及急性冠脉事件发生的病理生理基础。     

The association between blood group and the risk of vascular disease in Quebec blood donors

BackgroundThe association between antigens A and B and arterial thrombosis, such as coronary heart disease, cerebrovascular disease or peripheral vascular disease, is still unclear. We evaluated the association between blood groups and thrombotic events in a cohort of blood donors from the province of Quebec, Canada.ResultsAmong the blood donors, 64,686 had a known blood group and were linked with the provincial health databases. The mean age of these donors was 38 years. The Cox multivariate adjusted hazard ratio for coronary, cerebrovascular or peripheral diseases was 1.19 (95% confidence interval: 1.01–1.40) for subjects with blood group AB compared to those with blood group O. There were no statistically significant associations with other blood groups. Only among women aged ≥40 years did those with blood group A have a higher hazard ratio for coronary heart disease (1.40 [1.01–1.92]) than those with blood group O, after adjusting for other characteristics.DiscussionWhen compared to blood group O, only blood group AB was associated with a higher risk of hospitalisation or death because of thrombotic events such as coronary, cerebrovascular or peripheral diseases. However, the associations differed according to age and sex because only females aged ≥40 years with blood group A had a higher risk of coronary heart disease.     

Comparison of myeloma cell contamination of bone marrow and peripheral blood stem cell harvests

It could be speculated for patients with myeloma and other lymphoproliferative disorders that peripheral blood stem cells may be preferable to bone marrow for autologous transplantation because they may be less contaminated by neoplastic cells. To test this possibility, the immunoglobulin heavy chain gene rearrangement and limiting dilution polymerase chain reaction were used to sensitively quantify myeloma cells in bone marrow and peripheral blood stem cell collections, taken at a similar time, from eight patients with multiple myeloma. Levels of residual disease in the peripheral blood stem cell harvests were variable and did not reflect the tumour burden in the marrow. Peripheral blood stem cells contained 1.7 to 23 700-fold fewer myeloma cells compared with the bone marrow and would have resulted in reinfusion of 0.08 to 59 480-fold fewer myeloma cells based on total reinfused CFU-GM and 0.24 to 24 700-fold fewer myeloma cells based on total reinfused nucleated cells. Assuming that the proportion of clonogenic myeloma cells is equivalent, peripheral blood stem cells may be better than bone marrow as a source of haemopoietic stem cells for transplantation in multiple myeloma. The clinical follow-up suggested that patients transplanted with peripheral blood stem cells containing a low number of myeloma cells had better disease control than those transplanted with peripheral blood stem cells containing a high number.     

Successful Reduced-Intensity Hematopoietic Stem Cell Transplantation in Myelodysplastic Syndrome with Severe Coronary Artery Disease

A 60-year-old Japanese man with myelodysplastic syndrome (MDS) and effort angina was referred to our clinic for treatment of MDS. The patient was transfusion-dependent and displayed coronary artery disease (CAD) with 99% obstruction of the left anterior descending coronary artery. Treatment comprised reduced-intensity hematopoietic stem cell transplantation with administration of fludarabine phosphate (180 mg/m(2)) and busulfan (8 mg/kg), followed by allogeneic peripheral blood stem cell transplantation from an HLA-matched sister. The regimen was well tolerated, and engraftment occurred rapidly without any therapy-related complications, including cardiovascular attack. Sex chromosome analysis by fluorescence in situ hybridization revealed complete donor chimerism on day 29 for bone marrow cells and on day 59 for peripheral blood leukocytes. The patient became transfusion-independent on posttransplantation day 8. As of 22 months postoperatively, he remains well, with 100% Karnofsky performance status, a limited type of chronic graft-versus-host disease, and no recurrence of disease. The clinical course of the patient suggests that this preparative regimen allows safe allogeneic stem cell transplantation for MDS patients with severe CAD.