自体骨髓干细胞移植治疗糖尿病缺血性下肢血管病变临床研究

目的 观察自体骨髓干细胞移植治疗糖尿病(DM)下肢缺血性血管病的疗效及安全性.方法用自体骨髓干细胞移植治疗17例(28条)DM缺血性下肢血管病变患者,从髂骨取自体骨髓血300ml,体外分离单个核细胞悬浊液40 ml,多点肌注到缺血下肢.术后第1天至3个月观察各项指标.结果 移植后7～14 d患肢疼痛减轻,患足冷感改善;3个月疼痛明显缓解或消失,9条患肢行走间距延长.11例踝肱指数增加,溃疡面不同程度缩小;3例影像学复查示不同程度新生毛细血管形成.移植3个月后正中神经、腓总神经感觉及运动神经传导速度明显增加(P均<0.01);未出现并发症和明显不良反应.结论 自体骨髓干细胞移植治疗DM下肢缺血性血管病简单、安全、有效,能改善患者的生活质量.     

动员后PBMC移植用于糖尿病与非糖尿病下肢动脉缺血性疾病治疗的效果比较

目的探讨动员后外周血单个核细胞治疗糖尿病下肢动脉缺血性疾病的疗效及机制。方法选择糖尿病性下肢动脉缺血性疾病患者23例（糖尿病组）,非糖尿病性下肢动脉缺血性疾病患者36例（非糖尿病组）,两组均行骨髓干细胞动员后自体外周血单个核细胞移植治疗。计数两组动员前后外周血单个核细胞数、CD34＋细胞数,观察两组治疗前、治疗后7 d、治疗后4个月临床疗效评分（静息痛、冷感、无痛行走距离、组织缺损）。结果两组治疗后4个月静息痛、冷感、无痛行走距离、组织缺损评分均低于治疗前,P均〈0.05;两组治疗后疗效评分比较无统计学差异。糖尿病组动员前外周血单个核细胞数及CD34＋数量均明显低于非糖尿病组,动员后两组均升高且无显著差异。结论动员后自体单个核细胞移植治疗糖尿病下肢动脉缺血性疾病疗效确切,机制可能与动员后单个核细胞含有更早期的内皮干祖细胞并能提供干祖细胞增殖必需的微环境相关。     

自体骨髓干细胞移植治疗糖尿病足的临床疗效研究

目的探讨自体骨髓干细胞移植治疗糖尿病足的临床疗效。方法选择2010年3月—2013年6月我院收治的糖尿病足患者21例(23条血管),均进行自体骨髓干细胞移植治疗:首先获取自体骨髓血200~240 ml,分离出单个核细胞悬浊液3 ml,稀释后在患足侧小腿肌肉局部注射。21例患者均于移植前,移植后1个月、3个月进行下肢缺血性指标测定,并观察患者近期症状与体征变化。结果移植后1个月、3个月患者下肢疼痛评分、冷感评分、间歇性跛行评分均低于移植前,皮肤温度和经皮氧分压高于移植前(P0.05)。移植后3个月16例患者行数字血管造影(DSA)可见新生侧支血管形成;足部溃疡创面愈合13例,缩小3例,截肢(趾)平面降低5例。结论自体骨髓干细胞移植治疗糖尿病足效果较满意,能有效改善患者患足血液循环。     

自体外周血干细胞移植治疗糖尿病下肢血管病变的临床研究

目的 观察自体外周血干细胞移植治疗糖尿病下肢血管病变的临床疗效.方法 100例糖尿病下肢血管病变患者纳入本研究,其中48例自愿接受自体外周血干细胞移植治疗下肢血管病变的患者组成移植组,其余52例患者分配到药物组仅采用药物治疗下肢血管病变.治疗后6个月进行疗效评价.结果 移植组83.3%(40/48)的患者Fontaine分级好转,有效率显著高于药物组(P<0.05).移植组患肢皮温与经皮氧分压均明显升高,治疗前后差值与药物组差异有统计学意义(P<0.01).结论 自体外周血干细胞移植治疗糖尿病下肢血管病变是一种有效的手段.     

冠状动脉内多种自体骨髓干细胞移植治疗心绞痛对比研究

目的 对比评价骨髓单个核细胞、间充质干细胞和CD34+干细胞移植治疗心绞痛的安全性和有效性.方法 72例心绞痛患者,接受目前最佳药物治疗,随机分为单个核细胞组(24例)、间充质干细胞组(24例)和CD34+干细胞组(24例).常规前降支病变PCI术后,进行冠状动脉内自体骨髓干细胞移植,于冠状动脉病变近端注入骨髓干细胞.所有患者于术前和术后6个月进行二维超声、单光子体层扫描(SPECD和动态心电图检测,术中,术后3、6个月评价心肌梗死、心律失常等并发症和心绞痛的疗效.结果 未观察到因冠状动脉内注射而导致的心肌梗死、心肌酶升高、心肌穿孔、心包积液、室性心动过速或室颤发生,无严重不良事件发生.从治疗有效性指标心绞痛发作频率、硝酸甘油用量、运动时间及加拿大心血管学会心绞痛分级方面评价,CD34+干细胞组与前两组相比,差异具有统计学意义(均为P＜0.05,P＜0.01);前两组间差异无统计学意义(P＞0.05).结论 冠状动脉内注射自体骨髓干细胞治疗心绞痛是安全和有效的,其中CD34+干细胞移植优于骨髓间充质干细胞和骨髓单个核细胞.     

自体骨髓单个核细胞移植对肝硬化患者血清白蛋白的影响

目的探讨经肝动脉插管自体骨髓单个核细胞(BM-MNCs)移植对肝硬化患者血清白蛋白(ALB)的影响。方法 201例肝硬化患者中,131例进行自体骨髓单个核细胞移植,70例为对照。骨穿采集自体骨髓,分离纯化单个核细胞将其经肝动脉插管移植入肝脏。分别于移植后4、8、12及24周观察ALB变化情况,比较不同Child-Pugh分级肝硬化患者ALB的改变。结果移植组患者移植前血清ALB平均为(29.33±3.92)g/L,移植后第4、8、12、24周分别为(32.37±4.63)g/L、(32.82±4.84)g/L、(32.95±5.10)g/L和(32.22±5.87)g/L。移植后24周内血清ALB水平较移植前显著升高,而对照组则无明显变化,两组比较差异有统计学意义。移植组中,Child-PughA、B级患者血清ALB改善程度大于C级患者。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提高肝硬化患者血清ALB水平,对Child-PughA、B级患者改善明显。     

经冠状动脉自体骨髓单个核细胞移植治疗急性前壁心肌梗死的研究

目的观察经冠状动脉将自体骨髓单个核细胞(MBMC)移植治疗急性前壁心肌梗死的疗效。方法本实验为开放性、前瞻性、非随机、对照研究。选取40例急性前壁心肌梗死患者,根据患者的意愿分为干细胞移植组(20例,接受急诊经皮冠状动脉介入治疗(PCI)+标准药物+经冠状动脉注入骨髓单个核细胞治疗)和常规治疗对照组(20例,接受急诊PCI+标准药物治疗)。两组患者分别于术前、术后3个月、术后6个月进行6min步行试验、多普勒超声心动图9、9 mTc-MIBI心肌灌注显像检查并记录发病6个月内主要临床事件。结果同对照组相比,6min步行试验、超声心动图、心肌ECT术前与术后3个月时两组无明显差异P>0.05,术后6个月,干细胞移植组较对照组心功能改善明显P<0.05,差异有统计学意义。结论本研究提示,自体骨髓单个核细胞经冠状动脉移植修复急性心肌梗死是安全有效的,细胞移植所显示的改善心功能的效果,可能与心肌和血管再生,限制和逆转了心室重构有关。     

自体骨髓单个核细胞移植对急性前壁心肌梗死患者心功能的影响

目的观察经冠状动脉自体骨髓单个核细胞(MBMC)移植对急性前壁心肌梗死患者心功能的影响。方法选取40例急性前壁心肌梗死患者,根据患者的意愿分为干细胞移植组(20名,接受急诊PCI+标准药物+经冠脉注入骨髓单个核细胞治疗)和常规治疗对照组(20名,接受急诊PCI+标准药物治疗)。两组患者分别于术前、术后3个月、术后6个月进行6min步行试验、多普勒心脏超声、平衡法核素心血池显像(ERNA),并记录发病6个月内主要临床事件。结果同对照组相比,6min步行试验、超声心动图、ERNA术前与术后3个月两组差异无统计学意义(P>0.05),术后6个月移植组心功能改善明显(P<0.05),差异有统计学意义。结论自体骨髓单个核细胞经冠脉移植治疗急性心肌梗死近期可以改善患者心功能。     

自体骨髓单个核细胞移植治疗扩张型心肌病疗效观察

目的 观察扩张型心肌病患者经冠状动脉自体骨髓单个核细胞移植治疗的安全性及近中期疗效.方法 258例扩张型心肌病患者,传统治疗的基础上,根据是否行经冠状动脉自体骨髓单个核细胞移植分为移植组(n=71)和对照组(n=187).随访两组患者术前、术后1、3、6个月和1、2年超声心动图、动态心电图、6 min步行距离及心脏核素(SPECT)检查,记录年住院天数.结果 移植组6 min步行距离术后1个月明显优于对照组[(345±76)m比(286±104)m,P<0.05].术后各随访时间点比较,移植组均优于对照组(P<0.05).术后1个月,移植组左心窜射血分数(LVEF)明显高于对照组[(41.5±9.4)%比(37.3±6.6)%,P<0.05].术后2年时移植组LVEF略高于对照组,差异无统计学意义[(43.6±6.3)%比(43.2±6.0)%,P>0.05].术后3个月移植组缺血心肌节段数较术前减少,且较对照组少[分别为(2.0±1.0)个比(3.1±1.4)个和(2.0±1.0)个比(3.1±1.2)个,P均<0.05],而坏死心肌节段数移植前后无明显改变.两组患者牛存率比较,差异无统计学意义(95.4%比94.9%,P>0.05).但移植组患者年住院天数明显少于对照组[(23.6±13.4)d比(33.0±14.0)d,P<0.05].结论 经冠状动脉自体骨髓单个核细胞移植具有良好的安全性,能够提高扩张型心肌病患者的LVEF、增加6 min步行距离,减少年住院大数,且近期疗效显著,中期疗效与传统治疗相似.     

自体骨髓干细胞移植治疗糖尿病足13例报告

目的 观察自体骨髓干细胞移植治疗糖尿病足(DF)的疗效。方法 2003年3～12月，应用自体骨髓干细胞移植治疗13例DF患者。男7例，女6例；平均年龄70岁；患肢共15条，左7条和右8条。手术首先抽取自体骨髓350ml，从中分离出单个核细胞悬浊液约40ml，行下肢缺血肌肉内局部注射。结果 小腿疼痛缓解率为100％，足部疼痛改善率为84．6％。保肢率为80％。冷、凉感觉改善率为100％。1例间歇性跛行患者的行走距离由术前的50m延长到120m。7例患者的8条下肢的动脉造影，显示均有新生侧枝血管形成。踝部经皮氧分压测定，10例患者的12条下肢均高于目前临床上截肢的最低临界值20mm Hg。结论 对由于下肢远端动脉流出道差或年老体弱或伴发其他疾病等不能接受搭桥术的患者，自体骨髓干细胞移植治疗DF是一种有效的方法。     

Therapeutic Angiogenesis by Transplantation of Autologous Bone Marrow and Peripheral Blood Mononuclear Cells in Patients with Peripheral Arterial Disease

Recently, the effectiveness and safety of therapeutic angiogenesis by transplantation of autologous bone marrow mononuclear cells (BM-MNCs) to ischemic limbs have been reported. We investigated whether transplantation of peripheral blood mononuclear cells (PB-MNCs) would also be as effective as BM-MNC-transplantation in patients with peripheral arterial disease. BM-MNC-transplantation into unilateral ischemic limbs was performed in five patients, and both BM-MNC and PB-MNC-transplantation into bilateral ischemic limbs (BM-MNCs into severe ischemic limbs and the same number of PB-MNCs into contralateral less ischemic limbs) were performed in five patients. The number of CD34⁺ cells in PB-MNCs was ~100-fold less than that in BM-MNCs, while PB-MNCs secreted substantial amounts of vascular endothelial growth factor (VEGF) during a 24-hour incubation. There was no increase in the serum VEGF levels by BM-MNC-transplantation alone, while there was a significant increase in the serum VEGF levels after transplantation of both BM-MNCs and PB-MNCs. Two weeks after transplantation, the ankle-brachial index and transcutaneous oxygen pressure were significantly increased in BM-MNC-transplanted limbs, while there were no significant increases in these parameters in PB-MNC-transplanted limbs. In conclusion, autologous transplantation of BM-MNCs represents a new and promising strategy for clinical application designed to revascularize ischemic tissues, but there were no definite therapeutic effects of transplantation of PB-MNCs.     

Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats

BACKGROUND/AIMS: The autologous transplantation of bone marrow cells is a promising treatment for liver disease. Pluripotent bone marrow stem cells can differentiate into hepatocytes, but few reports address the therapeutic effect of transplanting these stem cells into damaged liver in vivo. Here, we transplanted bone marrow-derived mesenchymal cells (BMMCs) to test their effect in liver-injured rats. METHODS: Rat bone marrow cells were cultivated for 2 weeks in the presence or absence of hepatocyte growth factor (HGF), labeled with a fluorescent marker, and transplanted by injection into CCl(4)-injured rats. Blood samples collected 4 weeks later were analyzed for albumin production and transaminase levels. The amount of fibrosis was determined by histology. RESULTS: RT-PCR analysis detected alpha-fetoprotein and albumin mRNAs in BMMCs cultured with HGF for 2 weeks. Albumin protein was also produced in the BMMC cultures by a subpopulation of cells. Transplantation of the BMMCs into liver-injured rats restored their serum albumin level and significantly suppressed transaminase activity and liver fibrosis. These effects were not seen when the BMMCs were cultured without HGF. CONCLUSIONS: The transplantation of BMMCs cultured with HGF effectively treats liver injury in rats. This is a promising technique for autologous transplantation in humans with liver injury.     

Long-term effects of repeated autologous transplantation of bone marrow cells in patients affected by peripheral arterial disease

Long-term effects of autologous mononuclear bone marrow cell transplantation were studied in patients with severe peripheral arterial disease (PAD) and critical limb ischemia. Ten patients with end-stage disease were infused twice with autologous bone marrow cells and they completed the 12-month follow-up study. Substantial improvement of blood flow and increasing capillary densities were seen when compared with a concomitant control group comprising patients who did not enroll in the study. The ankle-brachial index (ABI) and pain-free walking distance improved significantly in treated patients. The improvement was sustained 12 months after treatment. These results confirm that the autologous bone marrow transplantation is an effective therapeutic strategy in critical limb ischemia.     

CD133＋细胞含量对自体骨髓干细胞移植治疗肝硬化疗效的影响

目的研究分离骨髓干细胞后CD133＋细胞含量对自体骨髓干细胞移植治疗肝硬化疗效的影响。方法回顾性分析自体骨髓干细胞移植治疗肝硬化病例39例,其中CD133＋细胞含量不足2%的22例,CD133＋细胞含量超过2%（含2%）的17例。分析上述病例术后2～4周的实验室检测指标。结果在CD133＋细胞含量不足2%的病例中,患者术后的血清总蛋白、碱性磷酸酶和白蛋白均较术前明显增高（P〈0.05）。在CD133＋细胞含量超过2%的病例中,患者术后的血清总蛋白和白蛋白较术前明显增高（P〈0.05）。结论自体骨髓干细胞移植可以有效的提升肝硬化患者血清总蛋白和白蛋白水平,本组病例中CD133＋细胞含量的不同并未明显影响术后患者血清总蛋白、白蛋白的恢复水平。自体骨髓干细胞移植可能影响胆汁的排泌。     

Marked decrease of plasma VEGF after implantation of autologous bone marrow mononuclear cells in a patient with critical limb ischemia--a case report

The authors performed autologous bone marrow mononuclear cells implantation (BMI) in a 79-year-old man with critical limb ischemia. After BMI, the resting pain of the ischemic leg improved gradually. They measured the plasma concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and serum hepatocyte growth factor (HGF) in the blood from bilateral femoral veins. Before BMI, the plasma VEGF and bFGF concentrations were much greater in the ischemic leg than in the other lower limb, but decreased to the same concentrations as those in the contralateral lower extremity after BMI. The large concentrations of the angiogenic factors VEGF and bFGF in plasma indicate the severity and extent of the leg ischemia. BMI resulted in lower levels of VEGF and bFGF, and this fall is the hallmark of the effectiveness of BMI in the treatment of peripheral artery disease.     

CD34~+细胞含量对自体骨髓干细胞移植治疗肝硬化疗效的影响

目的研究分离骨髓干细胞后CD34+细胞含量对自体骨髓干细胞移植治疗肝硬化疗效的影响。方法回顾性分析自体骨髓干细胞移植治疗肝硬化病例41例,其中CD34+细胞含量不足5%的27例,CD34+细胞含量超过5%(含5%)的14例。分析上述病例术后2～4周的实验室检测指标。结果在CD34+细胞含量不足5%的病例中,患者术后的血清总蛋白、白蛋白(Alb)、碱性磷酸酶(ALP)和血小板(PLT)均较术前明显增高(P<0.05)。在CD34+细胞含量超过5%的病例中,患者术后的血清总蛋白、Alb较术前明显增高(P<0.05)。术前CD34+细胞含量超过5%病例组的PLT平均值[(88.357±38.454)×109/L]明显低于CD34+细胞含量不足5%的病例组[(132.590±127.260)×109/L]。结论自体骨髓干细胞移植可以有效的提升肝硬化患者血清总蛋白和Alb水平,本组病例中CD34+细胞含量的不同并未明显影响术后患者血清总蛋白、Alb的恢复水平。自体骨髓干细胞移植可能影响胆汁的排泌。两组病例脾功能亢进程度不同可能是导致患者CD34+细胞含量差异的原因。     

Long-term marrow reconstitutive ability of autologous grafts in lymphoma patients using peripheral blood mobilized with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor compared to bone marrow

OBJECTIVES: The aim of this study was designed to compare the in vivo long-term hematopoietic potential of bone marrow and peripheral blood grafts. MATERIALS AND METHODS: Marrow progenitor cell recovery was assessed for up to 4 years in 227 patients. One hundred patients were treated for malignant lymphomas by autologous bone marrow transplantation (BMT) and 127 by peripheral blood progenitor cell transplantation (PBPCT). RESULTS: Marrow progenitor cell counts were decreased for several years with both bone marrow and peripheral blood grafts. They were not different according to the origin of the graft, despite the reduced duration of peripheral blood cell recovery observed after PBPCT. Granulocyte colony-stimulating factor (G-CSF) used for PB graft mobilization and after transplantation resulted in faster neutrophil recovery compared to granulocyte-macrophage colony-stimulating factor (GM-CSF) with no evidence of decreased marrow progenitor cell recoveries. On the other hand, postgraft administration of GM-CSF enhanced long-term colony-forming unit granulocyte-macrophage reconstitution only after BMT. Factors that influenced marrow progenitor cell reconstitution have been identified by univariate and multivariate analysis: age, gender, type of lymphoma, and postgraft administration of hematopoietic growth factors (HGF) for the whole patient group; gender, graft progenitor cell yields, and type of HGF (G-CSF vs GM-CSF) for the PBPCT group; and only type of HGF for the BMT group.Despite faster peripheral blood cell recovery, persistent deficiency of marrow progenitor cells was found several years after PBPCT, as observed after BMT. G-CSF-mobilized PBPCT resulted in faster neutrophil recovery compared to GM-CSF mobilization, with no difference in long-term hematopoietic reconstitution.     

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.     

骨髓单个核细胞移植对缺血性心肌病患者血浆利钠肽水平的影响

目的:观察骨髓单个核细胞(mononuclear bone marrow cell,MBMC)移植对缺血性心肌病患者左心功能及血浆利钠肽的影响。方法:36例缺血性心肌病患者分为细胞移植组24例和常规治疗组12例。结果:治疗3d后移植组及对照组心房利钠肽(atrial natriuretic peptide,ANP)、脑利钠肽(brain natriuretic peptide,BNP)均无明显变化,治疗7d后,移植组BNP下降了67.76%,对照组下降了24.1%;移植组ANP上升36.65%,而对照组下降14%,超声心动图结果显示:移植组左心室射血分数(LVEF)由(34.8±1.27)%升至(44.45±2.08)%(P<0.001),对照组LVEF由(36.20±3.80)%升至(38.97±2.76)%(P<0.05)。结论:MBMC经冠状动脉移植后早期(1周内)可明显改善心力衰竭患者的心功能,其机制之一可能为外源ANP生成而发挥的利钠、利尿、扩血管作用。     

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。