ObjectiveTo observe the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on blood glucose levels and diabetic retinopathy in diabetes mellitus (DM) rats. MethodA total of 45 healthy male Sprague-Dawley rats were randomly divided into normal control group (group A, 10 rats) and DM group (33 rats). Diabetic model was established in DM group by tail vein injection of streptozotocin.The DM group was further randomly divided into 3 groups (11 rats in each group), including group B (no transplantation), group C (hUCMSC was injected through tail vein) and group D (hUCMSC was injected into the vitreous). Blood glucose, retina wholemont staining and expression of brain derived neurotrophic factor (BDNF) in the retina were measured at 2, 4, 6, 8 weeks after hUCMSC injection. The blood glucose was significantly different between A-D groups before injection (t=-64.400, -60.601, -44.065, -43.872; P=0.000) BDNF expression was studied by real time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry staining. ResultsThe blood glucose was significantly different between A-D groups after hUCMSC injection (F=400.017, 404.410, 422.043, 344.109; P=0.000), and between group C and group B/D (t=4.447, 4.990; P < 0.01). Immuno-staining shown that BDNF was positive in ganglion cell layer (RGC) of group A, weak in group B while BDNF expression increased in group C/D. BDNF mRNA expression was significantly different between group B, C and D at 4, 6 and 8 weeks after hUCMSC injection (F=29.372, 188.492, 421.537; P=0.000), and between group B and C/D (t=66.781, 72.401, 63.880, 88.423, 75.120, 83.002; P < 0.01) by RT-PCR analysis. The BDNF mRNA expression was significantly different between C and D groups only at 8 weeks after hUCMSC injection (t=127.321, P=0.005). ConclusionsTail vein injection of hUCMSCs can significantly reduce the blood glucose levels of rats. Intravenous and intravitreal injection of hUCMSCs can increase the expression of BDNF.
【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 review the value of imaging assessment of stem cell transplantation in treatment for liver cirrhosis.Methods The related literatures in recent years were collected,and the applications of different radiological techniques and strategies of stem cell transplantation in treatment for liver cirrhosis were summarized.Results Stem cell transplantation in treatment for liver cirrhosis was feasible and effective. Radiological assessment could supply the prompt and accurate information for clinic to choose the proper therapeutic method.The curative effect could also be accurately assessed by radiological techniques.Conclusion Radiological examination is important for the assessment of stem cell transplantation in treatment for liver cirrhosis.
目的:观察血液病患者造血干细胞移植后外周血细胞参数的近期动态变化,了解骨髓恢复情况。方法:使用SE-9500血细胞分析仪对28例血液病患者造血干细胞移植前后血液进行检测,观察移植后一个月内各参数的变化。结果:28例外周血干细胞移植前后各细胞参数的观察发现,红细胞平均容积(MCV)、红细胞平均血红蛋白含量(MCH)、红细胞平均血红蛋白浓度(MCHC)和红细胞体积发布宽度(RDW-CV%)等参数其结果在干细胞移植前后进行比较,虽然有变化,但无显著性差异(Pgt;0.05);红细胞计数(RBC)、血红蛋白(HGB)、红细胞压积(HCT)、网织红细胞绝对数(RET)、低荧光强度网织红细胞百分率(LFR%)、高荧光强度网织红细胞百分率(HFR%)和中荧光强度网织红细胞百分率(MFR%)等参数变化较大,有显著性差异(Plt;0.05)。RBC、HGB和HCT在移植后第14天降至最低,以后逐渐升高;在干细胞移植后第7天RET＃、MFR％和HFR％降至最低,LFR％相对增高,随着干细胞移植后骨髓功能逐渐恢复,RET＃也随之升高,HFR在第14天升至最高,MFR在第21天升至最高。结论:观察干细胞移植后外周血细胞参数的变化,对了解干细胞移植后骨髓的恢复有一定的临床价值,本次结果表明HFR可作为了解骨髓恢复的早期指标。
【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.
ObjectiveTo observe the clinical features of cytomegalovirus (CMV) retinitis (CMVR)-related uveitis after hematopoietic stem cell transplantation (HSCT).MethodsA retrospective clinical study. From October 2015 to May 2020, 14 cases of 21 eyes of CMVR patients with CMVR after HSCT confirmed by the ophthalmological examination of The First Affiliated Hospital of Soochow University were included in the study. Among them, there were 5 males with 8 eyes and 9 females with 13 eyes. The average age was 35.12±12.24 years old. All the affected eyes were examined by slit lamp microscope combined with front lens and fundus color photography. At the same time, fluorescein fundus angiography (FFA) was performed to examine 10 eyes of 5 cases; 3 cases of 3 eyes were examined for inflammatory cytokines in aqueous humor. All eyes received intravitreal injection of ganciclovir; patients with a history of systemic CMV infection received intravenous infusion of ganciclovir/foscarnet. The retinal lesions in the eye were completely resolved or the aqueous CMV-DNA was negative as a cure for CMVR. The uveitis symptoms, signs, FFA manifestations and the test results of inflammatory factors in aqueous humor before and after the CMVR cure was observed. The follow-up time after CMVR was cured was 3-42 months, and the average follow-up time was 14.28±13.12 months.ResultsAll eyes with CMVR were diagnosed with retrocorneal dust and/or stellate keratic precipitates (KP), anterior chamber flare and cells, and varying degrees of vitreous flocculent opacity; the retina was typical of a mixture of hemorrhage and yellow-white necrosis like "scrambled eggs with tomatoes". After CMVR was cured, there were 16 eyes (71.4%, 10/14) in 10 cases with KP, anterior chamber flare, cell and vitreous opacity. FFA examination revealed that the majority of retinal leakage during the active period of CMVR was necrotic foci and surrounding tissues; after CMVR was cured, the majority of retinal leakage was the retina and blood vessels in the non-necrotic area. The test results of inflammatory factors in aqueous humor showed that interleukin (IL)-6, IL-8, and vascular endothelial cell adhesion molecules were significantly increased in the active phase of CMVR; after 3 months of CMVR cured, inflammatory factors did not increase significantly.ConclusionCMVR-associated uveitis after HSCT show as chronic panuveitis, with no obvious eye congestion, KP, anterior chamber flare, cell and vitreous opacity, and retinal vessel leakage which could exist for a long time (＞3 months).
ObjectiveTo observe the morphological and functional changes of retinal degeneration in mice with CLN7 neuronal ceroid-lipofuscinosis, and the therapeutic effects of glial cell derived neurotrophic factor (GDNF) and/or ciliary neurotrophic factor (CNTF) based on neural stem cells (NSC) on mouse photoreceptor cells. MethodsA total of 100 CLN7 mice aged 14 days were randomly divided into the experimental group and the control group, with 80 and 20 mice respectively. Twenty C57BL/6J mice aged 14 days were assigned as wild-type group (WT group). Mice in control group and WT group did not receive any interventions. At 2, 4, and 6 months of age, immunohistochemical staining was conducted to examine alterations in the distribution and quantity of cones, rod-bipolar cells, and cone-bipolar cells within the retinal of mice while electroretinography (ERG) examination was utilized to record scotopic a and b-waves and photopic b-wave amplitudes. At 14 days of age, the mice in the experimental group were intravitreally injected with 2 μl of CNTF-NSC, GDNF-NSC, and a 1:1 cell mixture of CNTF-NSC and GDNF-NSC (GDNF/CNTF-NSC). Those mice were then subdivided into the CNTF-NSC group, the GDNF-NSC group, and the GDNF/CNTF-NSC group accordingly. The contralateral eyes of the mice were injected with 2 μl of control NSC without neurotrophic factor (NTF) as their own control group. At 2 and 4 months of age, the rows of photoreceptor cells in mice was observed by immunohistochemical staining while ERG was performed to record amplitudes. At 4 months of age, the differentiation of grafted NSC and the expression of NTF were observed. Statistical comparisons between the groups were performed using a two-way ANOVA. ResultsCompared with WT group, the density of cones in the peripheral region of the control group at 2, 4 and 6 months of age (F=285.10), rod-bipolar cell density in central and peripheral retina (F=823.20, 346.20), cone-bipolar cell density (F=356.30, 210.60) and the scotopic amplitude of a and b waves (F=1 911.00, 387.10) in central and peripheral retina were significantly decreased, with statistical significance (P＜0.05). At the age of 4 and 6 months, the density of retinal cone cells (F=127.30) and b-wave photopic amplitude (F=51.13) in the control group were significantly decreased, and the difference was statistically significant (P＜0.05). Immunofluorescence microscopy showed that the NSC transplanted in the experimental group preferentially differentiated into astrocytes, and stably expressed CNTF and GDNF at high levels. Comparison of retinal photoreceptor nucleus lines in different treatment subgroups of the experimental group at different ages: CNTF-NSC group, at 2 months of age: the whole, central and peripheral regions were significantly different (F=31.73, 75.06, 75.06; P＜0.05); 4 months of age: The difference between the whole area and the peripheral region was statistically significant (F=12.27, 12.27; P＜0.05). GDNF/CNTF-NSC group, 2 and 4 months of age: the whole (F=27.26, 27.26) and the peripheral area (F=16.01, 13.55) were significantly different (P＜0.05). In GDNF-NSC group, there was no statistical significance at all in the whole, central and peripheral areas at different months of age (F=0.00, 0.01, 0.02; P＞0.05). ConclusionsCLN7 neuronal ceroid-lipofuscinosis mice exhibit progressively increasing degenerative alterations in photoreceptor cells and bipolar cells with age growing, aligning with both morphological and functional observations. Intravitreal administration of stem cell-based CNTF as well as GDNF/CNTF show therapeutic potential in rescuing photoreceptor cells. Nevertheless, the combined application of GDNF/CNTF-NSC do not demonstrate the anticipated synergistic protective effect. GDNF has no therapeutic effect on the retinal morphology and function in CLN7 neuronal ceroid-lipofuscinosis mice.
【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.