Objective To systematically review the effectiveness and safety of autologous implantation of stem cells for diabetic peripheral neuropathy (DPN). Methods Randomized controlled trials on relevant studies were retrieved in databases including CBM (1978-2011.6), CNKI (1979-2011.6), MEDLINE (1950-2011.6), PubMed (1950-2011.6), EMbase (1970-2011.6) and The Cochrane Library (Issue 3, 2011). References of the included studies were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assess the methodological quality of the included studies. Then, meta-analysis was performed using RevMan 5.0 software.Results Four RCTs involving 68 patients (136 limbs) were included, most of which were low in methodological quality. The results of meta-analysis indicated that, autologous stem cell therapy improved or even eliminated DPN symptoms including pain, numbness, and cold sensation in the limbs, intermittent limping, and rest pain. Compared with the routine therapy, autologous stem cell therapy improved tibial sensory nerve conduction velocity (MD=5.75, 95%CI 3.86 to 7.64, Plt;0.000 01), tibial motor nerve conduction velocity (MD=4.04, 95%CI 0.90 to 7.18, P=0.001), sural sensory nerve conduction velocity (MD=7.47, 95%CI 4.00 to 10.94, Plt;0.000 1), and sural motor nerve conduction velocity (MD=3.38, 95%CI 0.07 to 7.58, P=0.05), with no adverse reaction reported. Conclusion Current evidence shows that, autologous stem cell therapy is effective in treating DPN. Due to the lack of high quality studies, more high quality RCTs are needed to verify the above conclusion.
【摘要】 目的 探讨自体造血干细胞移植（autologous hematopoietic stem cell transplantation，auto-HSCT）治疗侵袭性NK/T细胞淋巴瘤的疗效。 方法 对我科2005年1月16日收治的1例侵袭性NK/T细胞淋巴瘤患者的造血干细胞移植和随访资料进行回顾性分析，并复习国内外相关文献。 结果 患者为37岁女性，诊断结外鼻型NK/T细胞淋巴瘤，系统性，经CHOAP和ICE方案化学疗法、手术、局部放射治疗控制病情良好后，采集自体骨髓造血干细胞，行auto-HSCT，预处理方案为全身放射治疗+ECy；移植+29 d造血功能即顺利重建；移植后密切随访，患者一直处于完全缓解，至今已存活67个月。 结论 auto-HSCT治疗侵袭性NK/T细胞淋巴瘤疗效肯定、可靠。【Abstract】 Objective To explore the therapeutic effect of autologous hematopoietic stem cell transplantation (auto-HSCT) on aggressive NK/T lymphoma. Methods The clinical data of one patient with aggressive NK/T lymphoma diagnosed in January 2005 were retrospectively analyzed, and the relevant domestic literatures were analyzed. Results This thirty-seven-year-old female patient had good disease control after undergoing chemotherapy with CHOAP and ICE regimens, surgery, and locoregional radiotherapy. After that, she had been collected enough bone marrow-derived hematopoietic stem cells, then underwent auto-HSCT with these cells. The conditioning regimen was TBI plus ECy. On the +29th day after transplantation,the hematopoietic reconstruction was successful. During the follow-up period, the patient was in complete remission status all along and her disease-free survival (DFS) was 67 months. Conclusion Auto-HSCT is effective on aggressive NK/T lymphoma.
【摘要】 目的 分析异基因造血干细胞移植术（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后并发毛细血管渗漏综合征（capillary leak syndrome，CLS）的发生率、危险因素和结局，并探讨其防治措施。 方法 回顾性分析2005年6月-2011年2月住院的allo-HSCT术后14例并发CLS的临床资料。 结果 CLS发生率为9.2%（14/152）。年龄、性别、诊断、HLA配型、预处理、CD34+细胞量、粒细胞集落刺激因子（granulocyte colony-stimulating factor，G-CSF）用量、植入时间均不能认定为造血干细胞移植后CLS诱发因素。 结论 HSCT术后CLS诱因尚不清楚，采用限水、减量G-CSF、使用糖皮质激素和羟乙基淀粉等措施及时治疗，有助于控制CLS。【Abstract】 Objective To study the occurrence rate, risk factors and outcomes of capillary leak syndrome (CLS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and discuss its prevention and treatment. Methods We retrospectively analyzed the clinical records of 14 allo-HSCT recipients complicated with CLS from June 2005 to February 2011. Results Fourteen out of 152 patients developed CLS with a cumulative incidence of 9.2 %. None of the 8 clinical parameters including age, gender, underlying disease, donor type, conditioning regimen, CD34+ cell dose, granulocyte colony-stimulating factor (G-CSF) dosage, and days to neutrophil engraftment could be identified as risk factors for the occurrence of CLS. Conclusions Risk factors for CLS after allo-HSCT have not been fully established. Restriction of water intake, administration of corticosteroids and hydroxyethyl starch can be beneficial for patients with CLS.
【摘要】 目的 分析异基因造血干细胞移植术（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后出血性膀胱炎（hemorrhagic cystitis，HC）相关的危险因素，动态监测受者尿BK病毒（BK virus，BKV），分析其与HC发病的关系。 方法 回顾性分析2003年3月-2008年1月期间接受allo-HSCT的121例患者的资料，选择8个临床参数[年龄、性别、疾病类型、移植时疾病状态、供者类型、预处理方案、急性移植物抗宿主病（acute graft-versus-host disease，aGVHD）、aGVHD的预防方案]作COX回归分析。采用SYBR Green染料实时荧光定量聚合酶链反应法对2006年9月-2008年1月42例allo-HSCT患者尿BKV载量进行动态监测，分析被检查者尿液BKV基因载量与HC发生以及严重程度的关系。 结果 121例患者中有24例发生HC，发病时间为术后0~63 d，中位时间40 d；持续时间7~150 d，中位时间22 d。Ⅱ~Ⅳ度aGVHD为HC的独立危险因素[RR=8.304，95%CI（1.223，56.396），P=0.030]。allo-HSCT受者尿液中BKV检出率为100%（42/42）。与正常人及未发生HC的allo-HSCT受者相比，HC患者尿中BKV基因载量具有更高平均峰值。 结论 Ⅱ~Ⅳ度aGVHD，尿中BKV DNA高载量与HC的发生有相关性。【Abstract】 Objective To identify the risk factors for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and define the quantitative relationship between BK virus (BKV) DNA load with HC. Methods The medical records of 121 patients undergoing allo-HSCT from March 2003 to January 2008 were retrospectively analyzed. Eight clinical parameters were selected for COX regression analysis, including age, sex, underlying disease, disease status at transplant, donor type, conditioning regimen, acute graft-versus-host disease (aGVHD), and GVHD prophylaxis. From September 2006 to January 2008, mid-stream urine samples were continuously collected from 42 patients with allo-HSCT. SYBR green real-time polymerase chain reaction, technique was utilized to define the quantitative relationship between BKV DNA load and HC. Results Twenty-four out of 121 patients developed HC. The median time of onset was 40 days after HSCT, ranged from 0 to 63 days. The disease lasted for 7 to 150 days, with a median duration of 22 days. Grade Ⅱ-Ⅳ aGVHD [RR=8.304, 95% CI (1.223,56.396); P=0.030] was identified as an independent risk factor for the occurrence of HC. BKV excretion was detected in 100% (42/42) of the recipients of allo-HSCT. When compared with asymptomatic patients and allo-HSCT recipients without HC, patients with HC had a significantly higher mean peak BKV DNA load. Conclusions Patients are at an increased risk of developing HC if they have grade Ⅱ-Ⅳ aGVHD. A correlation between the load of BKV and incidence of HC may exist.
【摘要】 目的 探讨对自体造血干细胞移植（autologous hematopoietic stem cell transplantation，auto-HSCT）后复发的非霍奇金淋巴瘤患者再进行异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation，allo-HSCT）治疗的临床疗效。 方法 收集2000年1月-2010年12月难治性恶性淋巴瘤采用auto-HSCT后复发患者11例，病程27个月~6.5年。所有患者在auto-HSCT前均为复发难治性病例，auto-HSCT后，完全缓解8例，部分缓解3例，自体移植后中位复发时间15个月，患者复发后采用异基因亲缘造血干细胞移植，人类白细胞抗原（human leukocyte antigen，HLA）全相合（6/6）6例，5/6相合3例，4/6相合2例；性别相同6例，性别不同5例。预处理方案为FBC方案，即氟达拉滨30 mg/m2 1~5 d，白消安12~14 mg/kg分4 d口服，环磷酰胺120 mg/kg分2 d使用。移植物均为外周血造血干细胞加骨髓。移植物抗宿主病（graft-versus-host disease，GVHD）的预防：HLA全相合采用环孢素+短程甲氨蝶呤+吗替麦考酚酯，不全相合采用抗胸腺细胞球蛋白+环孢素+短程甲氨蝶呤+吗替麦考酚酯。 结果 11例患者全部获得造血重建，急性GVHD发生6例（54.55%），其中Ⅰ度、Ⅱ度4例，Ⅲ度、Ⅳ度各1例；1例Ⅳ度GVHD因合并感染死亡，5例均得到有效控制；发生慢性GVHD 7例（63.64%），其中有2例急性GVHD转为慢性，4例局限型，3例广泛型。随访8个月~9年，有4例分别于移植后8、15、21、34个月疾病复发，另外6例仍生存。 结论 allo-HSCT对于auto-HSCT后复发的非霍奇金淋巴瘤患者仍是一种有效的挽救性治疗手段。【Abstract】 Objective To explore the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on relapsing non-Hodgkin′s lymphoma after autologous stem cell transplantation (auto-HSCT). Methods The clinical data of 11 patients with recurrent non-Hodgkin′s lymphoma after auto-HSCT from January 2000 to December 2010 were collected, including nine males and 2 females with the median age of 39 years (13-48 years old), and the median duration of the disease was 3 years (27 months-6.5 years). All patients were relapsed or refractory cases. After auto-HSCT, complete remission was found in 8 and partial remission was in 3. The recurrence median time after auto-HSCT was 15 months. The patients underwent allo-HSCT after the recurrence of the disease. In the 11 patients, human leukocyte antigen (HLA) full matched (6/6) in 6, 5/6 matched in 3, and 4/6 matched in 2; the same gender in 6 and different gender in 5. FBC conditioning regimen: fludarabine 30 mg/m2 for 1-5 days, BU 12-14 mg/kg in 4 days of oral, CY 120 mg/kg in 2 days. Grafts are peripheral blood stem cells plus bone marrow. Prevention of graft-versus-host disease (GVHD): HLA full-matched by CsA+short-term MTX+MMF and mismatched by ATG+CsA+short-term MTX+MMF. Results All of the 11 patients received hematopoietic reconstruction, acute GVHD occurred in 6 cases (54.55%), including degree Ⅰ plus Ⅱ in 4, degree Ⅲ in 1 and degree Ⅳ in 1. One patient died of infection due to degree Ⅳ GVHD, and the rest had been effectively controlled. Chronic GVHD occurred in 7 patients (63.64%); limited type was in 4 in and extensive type was in 3. During the follow-up period of 8 months-9 years, 4 patients relapsed 8, 15, 21, and 34 months after transplantation, and the other 6 patients was still alive. Conclusion Allo-HSCT is effective on relapsing non-Hodgkin′s lymphoma after auto-HSCT.
【摘要】 目的 了解人工肝支持系统抢救造血干细胞移植合并重症肝静脉闭塞病的临床疗效。 方法 对2002年1月-2010年12月因造血干细胞移植并发重症肝静脉闭塞病的6例患者，利用人工肝支持系统，选用血浆置换程序进行血浆置换。 结果 6例患者经血浆置换治疗后，胆红素均明显下降，3例最终恢复，2例因肝功能再次恶化死亡，1例死于严重混合性感染。 结论 人工肝支持系统抢救造血干细胞移植合并重症肝静脉闭塞病是一种新的尝试，是有效和可靠的。【Abstract】 Objective To explore the therapeutic efficacy of artificial liver support system on severe hepatic veno-occlusive disease accompanied with hematopoietic stem cell transplantation. Methods Between January 2002 and December 2010, six patients with severe hepatic veno-occlusive disease accompanied with hematopoietic stem cell transplantation underwent plasma exchange with plasma exchange procedures using artificial liver support system. Results After plasma exchange treatment, the bilirubins of six patients significantly decreased; three patients eventually recovered, two died because of liver function deteriorated again, and one died of severe mixed infections. Conclusion Artificial liver support system is effective and reliable for hematopoietic stem cell transplantation accompanied with severe hepatic veno-occlusive disease.
Objective To explore the treatment effect of bone marrow mesenchymal stem cells( BMSCs)transplantation in ratmodel of bleomycin-induced pulmonary fibrosis. Methods BMSCs fromten-day-old SDmale rat were cultured and marked with 4, 6-diamidino-2-phenylindole( DAPI) . Seventy female SD rats were randomly divided into four groups. Group A( n = 21) was intratracheally injected with saline as control. Group B( n = 21)were intratracheally injected with BLMA5 to establish pulmonary fibrosis. Group C( n = 21) was injected with BLMA5 intratracheally and BMSCs intravenously via tail vein simultaneously. Group D( n = 7) was injected with BMSCs 14 days after BLMA5 injection. The rats were sacrificed on 7th, 14th and 28th day respectively( rats of group D were on28th) . HE and Masson stainings were performed to observe lung pathological changes. Fluorocyte marked with DAPI was analyzed by fluorescent microscope. Sex determining region Y( SRY) gene were detected by PCR. The lung levels of HYP, tumor necrosis factor-α( TNF-α) and transforming growth factor-β1 ( TGF-β1 ) were measured by ELISA. Results ( 1) In group C and D, BMSCs marked with DAPI were detected in lung frozen section on 7th, 14th and 28th day, and SRY gene of male rats were detected by PCR. ( 2) Alveolitis was most obvious on 7th day and pulmonary fibrosis was most severe on 28th day in group B compared to other three groups( P lt;0. 05 or 0. 01) . Alveolitis and pulmonary fibrosis in group C and D were significantly alleviated compared to group B( P lt; 0. 05) , but still more severe than group A( P lt; 0. 05 or 0. 01) , which in group D was more severe compared to group C( P lt;0. 05) . ( 3) HYP level in group B, coincided with fibrosis, began to increase on7th day and reached the peak on 28th day, significantly higher than other three groups( P lt;0.05 or 0. 01) . TNF-αlevel in group B was highest on 7th day, then descended, which was significantly higher than group A and C on 14th day and not obviously different from other three groups on 28th day. TGF-β1 level in group B was highest on 28th day which was different significantly fromother three groups. Conclusion BMSCs can colonize in the recipient lung tissue and effectively prevent the development of pulmonary fibrosis of rats induced by BLMA5, especially in the early stage.
Abstract： Objective To study the effect of different numbers of bone marrow mesenchymal stem cells（MSCs） transplanted into rats with pulmonary arterial hypertension （PAH）induced by monocrotaline（MCT）and their influence on the expression of endothelin-1（ET-1）. Methods Forty healthy male Wistar rats（weight，from 180 to 250 g） were divided into four groups by random number table（n=10）：group A：Wistar rats were intraperitoneally injected with MCT 60 mg/ kg， and then injected with 1×106 MSCs via the external jugular vein；group B：Wistar rats were intraperitoneally injected with MCT 60 mg/kg，and then injected with 5×105 MSCs via the external jugular vein；MCT group：Wistar rats were intraperitoneally injected with MCT 60 mg/kg， and then injected with equal amount of PBS via the external jugular vein； control group：Wistar rats were intraperitoneally injected with equal amount of saline and then injected with equal amount of PBS via the external jugular vein. Four weeks after MSCs transplantation，right ventricular systolic pressure（RVSP） and ventricular weight ratio of right ventricle/ （left ventricle＋ventricular septum）were measured. Histomorphology of lung tissue was observed. Genetic expression of ET-1 in lungs and serum peptide of ET-1 were also measured. Results Four weeks after MSCs transplantation，both RVSP and ventricular weight ratio decreased significantly in rats of group Acompared with those of MCT group（RVSP：35.8±4.2 mm Hg vs. 47.2±10.1 mm Hg，P＜ 0.01； ventricular weight ratio：0.357±0.032 vs. 0.452±0.056，P＜0.01）， but these two parameters didn’t decrease significantly in rats of group B（P＞ 0.05）. By histopathological staining， the percentage of medial wall thickness of the pulmonary arterioles was significantly less in rats of group A than that of MCT group（19.7%±3.0% vs. 26.8%±3.6%， P＜ 0.01）. There was no statistical difference in the percentage of medial wall thickness of the pulmonary arterioles between group B and MCT group. Reverse transcriptase-polymerase chain reaction （RTase-PCR）results showed that ET-1messenger ribonucleic acid（mRNA）expression was highest in MCT group and MSCs transplantation significantly decreasedits expression in group A， while its expression was similar between group B and MCT group. The expression ofET-1 in plasma was also significantly decreased in group A than that in MCT group. Conclusion Intravenous MSCs transplantation can significantly inhibit MCT-induced PAH，and reduce both ET-1 mRNA expression in lung and ET-1 peptide level in plasma. It’s a better choice to transplant 1×106 MSCs to inhibit PAH in rats.
Abstract： Objective To investigate the effects of hepatocyte growth factor（HGF）gene transfected bone marrow mesenchymal stem cells （MSCs）transplantation in pigs with chronic ischemic heart disease. Methods MSCs were isolated from pig bone marrow by density gradient centrifugation and adherent cell culture, purified, and determined by cellsurface antigens（CD34, CD44, CD71, Ⅷ factor and desmin）. MSCs were transfected by adenovirus expressing hepatocyte growth factor（AdHGF）, and the influence of HGF on the biological characteristics of MSCs was tested. The pig model of chronic myocardial ischemia was established by placing Ameroid ring inside the left circumflex coronary artery via leftthoracotomy. A total of 40 pigs were randomly divided into 5 groups （n=8） and were injected 5×106/ml MSCs＋ 4×109 pfu 200 μl AdHGF （MSCs＋ AdHGF group）, 4×109 pfu 200 μl AdHGF （AdHGF group）, 5×106/ml MSCs 200 μl（MSCs group），4×109 pfu 200 μl AdNull （AdNull group）and 1 ml saline（control group） into the ischemic myocardiumrespectively. Echocardiogram, digital subtraction angiography （DSA） of coronary artery, single photon emission computed tomography（SPECT） myocardial perfusion imaging and cardiomyocyte apoptosis were examined after 4 weeks. Results Positive CD44 and CD71 and negative CD34, Ⅷ factorand desmin were detected in MSCs by flow cytometer. HGF had a b influence on stimulating the proliferation and differentiation of MSCs. Echocardiogram examination showed that left ventricular end-diastolic volume（LVEDV），left ventricular ejection fraction（LVEF），fractional shortening（FS）of MSCs＋ AdHGF group were significantly increased after treatment （P＜ 0.05）. DSA detection showed that ischemic neovascularization of MSCs＋ AdHGF group was significantly higher than those of AdHGF group and MSCs group （P＜ 0.05）. SPECT showed that the left ventricular myocardium of MSCs＋ AdHGF group appeared thickened,myocardial perfusion was significantly improved and the myocardial motion was significantly increased （P＜ 0.05）. Vascular density of MSCs＋ AdHGF group was significantly higher than those of AdHGF group and MSCs group by HE stain of myocardium ［（39.4±1.2）/ HPF vs. （36.5±1.4）/ HPF and（34.5±1.7）/ HPF，P＜ 0.05］. Cardiomyocyte apoptosis rate of MSCs＋ AdHGF group was significantly lower than those of AdHGF group and MSCs group by TUNEL stain （P＜ 0.05）. Conclusion Combination transplantation can promote the angiogenesis of chronic ischemic myocardium, inhibit cardiomyocyte apoptosis and improve heart function in pigs with chronic ischemic heart disease. The effect of HGF gene transfected MSCs transplantation is better than that of MSCs or HGF transplantation alone.