Cotransplanted bone marrow derived mesenchymal stem cells (MSC) enhanced engraftment of hematopoietic stem cells in a MSC-dose dependent manner in NOD/SCID mice

Transplantation of marrow-derived mesenchymal stem cells (MSCs), expanded by culture in addition to whole bone marrow, has been shown to enhance engraftment of human hematopoietic stem cells (HSCs). Our hypothesis was that there might be an optimum ratio range that could enhance engraftment. We examined the percent donor chimerism according to the ratio of HSCs to MSCs in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. We tested a series of ratios of co-transplanted CD34(+) -selected bone marrow cells, and marrow-derived MSCs into sublethally irradiated NOD/SCID mice. In all experiments, 1x10(5) bone marrow derived human CD34(+) cells were administered to each mouse and human MSCs from different donors were infused concomitantly. We repeated the procedure three times and evaluated engraftment with flow cytometry four weeks after each transplantation. Serial ratios of HSCs to MSCs were 1:0, 1:1, 1:2 and 1:4, in the first experiment, 1:0, 1:1, 1:2, 1:4 and 1:8 in the second and 1:0, 1:1, 1:4, 1:8 and 1:16 in the third. Cotransplantation of HSCs and MSCs enhanced engraftment as the dose of MSCs increased. Our results suggest that the optimal ratio of HSCs and MSCs for cotransplantation might be in the range of 1:8-1:16; whereas, an excessive dose of MSCs might decrease engraftment efficiency.     

Co-transplantation of human mesenchymal stem cells promotes human CD34+ cells engraftment in a dose-dependent fashion in NOD/SCID mice

Mesenchymal stem cells (MSCs) have recently been identified and characterized in humans. Moreover, MSC secrete cytokines that can support hematopoietic progenitor growth. In the present study, we evaluated whether the efficacy of hematopoietic stem cell transplantation is improved by their co-transplantation with MSC, and whether this is positively correlated with the dose of infused MSCs. Accordingly, irradiated NOD/SCID mice were transplanted with 1 x 10(5) human CD34+ cells in the presence or absence of culture expanded MSCs (1 x 10(6) or 5 x 10(6)). We evaluated human hematopoietic cell engraftment by flow cytometry and assessed MSC tissue distributions by fluorescence in situ hybridization. We found that CD45+ and CD34+ cell levels were significantly elevated in a dose-dependent manner in co-transplanted mice 4 weeks after transplantation. The engraftments of CD33+ and CD19+ cells also increased dose-dependently. However, the engraftment of CD3+ cells did not increase after co-transplantation with MSCs. Human Y chromosome+ cells were observed in multiple tissues and were more frequently observed in mice co-transplanted with 5 x 10(6) rather than 1 x 10(6) MSCs. These results suggest that MSCs are capable of enhancing hematopoietic cell engraftment and distribution in multiple organs in a dose-dependent fashion.     

Pre-engraftment syndrome in hematopoietic stem cell transplantation

The clinical findings of fever and skin rash with or without evidence of fluid retention, which mimic engraftment syndrome, have been observed during the pre-engraftment period in patients undergoing hematopoietic stem cell transplantation. In order to characterize this newly observed clinical syndrome called pre-engraftment syndrome (pES), we retrospectively analyzed the clinical records of 50 patients. Three out of 14 patients (23.1%) who underwent cord blood stem cell transplantation developed non-infectious fever, skin rash, and tachypnea 4-15 days prior to neutrophil engraftment. Two patients spontaneously recovered with fluid restriction and oxygen inhalation. One patient died of a complicated pulmonary hemorrhage in spite of aggressive supportive therapy and steroid treatment. Four out of 23 patients (17.4%) who underwent allogeneic bone marrow transplantation developed non-infectious fever and skin rash 4 to 5 days prior to neutrophil engraftment. All four of these patients recovered with only steroid treatment. These characteristic findings were not observed in patients who had undergone autologous peripheral blood stem cell transplantation. Interestingly, the speed of neutrophil engraftment was significantly faster for the patients suffering from pre-engraftment syndrome. The close observation and further pathophysiological research are required to better understand this syndrome.     

骨髓间充质干细胞在致敏与非致敏BALB/c小鼠造血干细胞移植中的应用

背景：造血干细胞移植对多种疾病具有治疗作用,但其取材不便,且细胞数量受年龄限制等原因,故而应用具有一定局限性。 目的：探索骨髓间充质干细胞在致敏与非致敏BALB/c小鼠造血干细胞移植中的应用价值。 方法：将BALB/c小鼠骨髓细胞在体外进行分离,采用贴壁培养的方法获得间充质干细胞,使用流式细胞仪对细胞表面的分子标记进行检测。应用异基因脾细胞输注方法建立致敏动物模型,用绿色荧光染料标记骨髓间充质干细胞,分别移植到致敏和非致敏的受体小鼠体内,并在移植后的不同时间点对间充质干细胞的归巢情况进行检测。对致敏BALB/c小鼠进行照射预处理,联合应用异基因骨髓细胞与同基因间充质干细胞移植,观察BALB/c小鼠的生存情况。 结果与结论：移植48 h后,间充质干细胞在致敏受体和非致敏受体小鼠分别归巢于脾脏和骨髓。在造血干细胞的移植实验中,致敏BALB/c小鼠接受异基因骨髓细胞与同基因骨髓间充质干细胞联合移植,结果显示致敏BALB/c小鼠全部在移植后12-15 d死亡,生存的中位时间是14 d,而仅接受异基因骨髓细胞移植的致敏BALB/c小鼠的中位生存时间为13 d。说明细胞移植后在致敏受体内间充质干细胞主要归巢为脾脏和骨髓,联合应用间充质干细胞移植对异基因造血干/祖细胞植入致敏受体体内并没有起到有效的促进作用。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

携带人端粒酶反转录酶基因脐血间充质干细胞移植治疗肺动脉高压

背景：保护机体肺血管的内皮细胞,是降低肺循环压力,预防肺动脉高压的重要环节。 目的：观察携带人端粒酶反转录酶基因的脐血间充质干细胞移植对大鼠肺动脉高压的治疗作用。 方法：体外进行脐血间充质干细胞的培养及纯化,在腺病毒介导下使人端粒酶反转录酶基因成功导入脐血间充质干细胞。将60只SD大鼠随机分成3组：肺动脉高压组、空腺病毒组、腺病毒转染组,每组20只,腹腔注射野百合碱进行肺动脉高压模型复制后,于颈内静脉分别注射1 mL的伊戈尔低糖培养基(L-DBEB),1 mL (1.5×1010 L-1)脐血间充质干细胞悬液,1 mL(1.5×1010 L-1)腺病毒介导下人端粒酶反转录酶基因转染的脐血间充质干细胞悬液。移植21 d后检测各组大鼠血流动力学水平、血浆内皮素1水平以及右心室的肥大指数。 结果与结论：各组大鼠动脉血压差异无显著性意义(P > 0.05);与肺动脉高压组及空腺病毒组比较,腺病毒转染组大鼠肺动脉收缩期压力、平均肺动脉压均降低,差异有显著性意义(P < 0.05);腺病毒转染组大鼠右心室肥大指数与肺动脉高压组及空腺病毒组相比较,差异均无显著性意义(P > 0.05);腺病毒转染组大鼠血浆内皮素1水平明显低于肺动脉高压组及空腺病毒组,差异有显著性意义(P < 0.05)。结果表明携带人端粒酶反转录酶基因的脐血间充质干细胞移植后,能够改善大鼠机体血流动力学异常状态,还可以保护机体血管内皮细胞。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

脐血间充质干细胞移植在卵巢癌化疗损伤中的作用

背景:研究证实,脐血间充质干细胞对多种损伤细胞有修复功能。目的:探讨脐血间充质干细胞移植在卵巢癌化疗性损伤中的作用。方法:健康级成年雌性Wistar大鼠60只,随机分为正常对照组,损伤组及治疗组,每组20只。对照组不做任何处理,损伤组及治疗组建立大鼠卵巢癌化疗性损伤模型。模型成功后对照组尾静脉注射生理盐水,损伤组注射紫杉醇,治疗组在损伤组基础上给予脐血间充质干细胞移植。移植后2周,应用RT-PCR检测卵巢癌组织XAF1、Survivin mR NA的表达,Western blot检测卵巢癌组织中XAF1、Survivin蛋白的表达,TUNEL法检测卵巢癌细胞凋亡情况。结果与结论:(1)与损伤组比较,治疗组肿瘤组织XAF1 mR NA和蛋白表达显著上调,凋亡抑制蛋白Survivin mR NA和蛋白表达显著下调(P<0.05);(2)损伤组卵巢组织结构较对照组明显破坏,有大面积的出血坏死区域,治疗组损伤程度较损伤组明显减轻;(3)与损伤组比较,治疗组卵巢癌细胞凋亡率明显升高(P<0.05);(4)结果表明,脐血间充质干细胞移植可以促进卵巢癌化疗性损伤大鼠卵巢组织的修复,XAF1、Survivin在肿瘤新生血管形成及卵巢癌细胞凋亡过程中发挥了作用。     

人脐带间充质干细胞移植治疗系统性红斑狼疮

背景：系统性红斑狼疮是一种以多器官或多系统病变和血清中出现多种自身抗体为特征的自身免疫性疾病,目前缺乏有效的治疗方案,而理论上间充质干细胞可用于治疗系统性红斑狼疮。目的：观察人脐带间充质干细胞移植治疗系统性红斑狼疮小鼠的疗效。方法：分离培养人脐带间充质干细胞,并用深红色荧光DiR标记细胞。实验小鼠分5组：正常对照组(C57BL小鼠),模型对照组(C57BL/lpr小鼠),低、中、高剂量脐带间充质干细胞治疗组(C57BL/lpr小鼠),每组10只。各治疗组通过尾静脉注射低、中、高剂量(2×10⁶,1×10⁶,0.5×10⁶个)脐带间充质干细胞,每周1次,连续3周,治疗结束采血测抗核抗体、抗组蛋白抗体、抗双链DNA抗体变化,定量PCR检测OPG和Foxp3基因表达的变化。结果与结论：细胞移植3次后,外周血抗核抗体、抗组蛋白抗体、抗双链DNA抗体均明显下降,CD4⁺CD25⁺T细胞明显升高,OPG和Foxp3基因表达也明显升高,接近正常对照组,与模型对照组相比差异均有显著性意义(P < 0.01)。结果表明人脐带间充质干细胞能使C57BL/lpr小鼠的各项相关指标恢复到C57BL正常鼠水平,以高剂量治疗组效果最明显。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

脐血间充质干细胞移植修复急性肠缺血再灌注损伤

BACKGROUND:Bone marrow mesenchymal stem cells can repair intestinal ischemia-reperfusion injuny by interfering inflammatory reactions after intestinal ischemia-reperfusion to protect intestinal barrier functions. In recent years, umbilical cord blood mesenchymal stem cells are gradually used as a substitute source of bone marrow mesenchymal stem cells. OBJECTIVE:To investigate the effects of umbilical cord blood mesenchymal stem cells on acute intestinal ischemia-reperfusion injury. METHODS:Umbilical cord blood mesenchymal stem cells were induced, isolated in vitro and tracked by CM-DiI fluorescent labeling. Sixty-three Sprague-Dawley rats were equivalently randomized into three groups: control group received normal saline enema, intestinal ischemia-reperfusion injury group with ethanol diluted trinitro-benzene-sulfonic acid and transplantation group administrated with 1×10¹⁰/L umbilical cord blood mesenchymal stem cell suspension via the tail vein at 1 hour after trinitro-benzene-sulfonic acid modeling. At 3 days after transplantation, colon tissues were removed in each group to observe pathological changes of the intestinal tract by hematoxylin-eosin staining. Besides, expression of leptin mRNA in the colon tissues and cyclooxygenase-2 in the mucosa were detected by RT-PCR and immunohistochemistry method, respectively. RESULTS AND CONCLUSION:Transplanted umbilical cord blood mesenchymal stem cells distributed in the intestinal lymphoid tissue and among glandular epithelial cells, suggesting that these stem cells might be involved in the process of intestinal ischemia-reperfusion injury repair. Compared with the control group, intestinal injury in the injury group was significantly aggravated, and most intestinal epithelial cells shed; and the transplantation group appeared to have significantly reduced intestinal damage and significantly less cell shedding. Expression of leptin mRNA was significantly higher in the injury group than the transplantation group followed by the control group, and there were significant differences among the three groups (P < 0.05). Additionally, expression of cyclooxygenase-2 in the injury group was significantly higher than that in the control group (P < 0.05); compared with the injury group, expression of cyclooxygenase-2 was significantly lower in the transplantation group (P < 0.05). To conclude, leptin and cyclooxygenase-2 may be involved in acute intestinal ischemia-reperfusion injury, and umbilical cord blood mesenchymal stem cell transplantation significantly lessens intestinal ischemia-reperfusion injury, which provides an experimental basis for human treating acute intestinal ischemic injury.     

脐血间充质干细胞移植治疗多发性肌炎/皮肌炎：Th细胞因子的变化

背景：近年来,应用干细胞治疗免疫性疾病已成为研究热点,国内外有关脐血间充质干细胞移植治疗多发性肌炎/皮肌炎的报道较少。目的：观察脐血间充质干细胞移植治疗多发性肌炎/皮肌炎患者血清干扰素γ、白细胞介素4、白细胞介素17水平变化,探讨Th细胞因子在多发性肌炎/皮肌炎发生发展中的免疫机制。方法：81例多发性肌炎/皮肌炎患者,其中44例为常规治疗组,给予糖皮质激素联合免疫抑制剂治疗,37例为脐血间充质干细胞移植组,静脉输注脐血间充质干细胞(3.5-5.2)×10⁷,用药方案与常规治疗组相同。随访治疗后1,3,6 个月肌酸激酶、肌力变化及治疗后3,6个月肺部影像学改变,并在治疗前及治疗后3,6个月检测移植组Th细胞因子水平。结果与结论：①两组治疗后1,3,6个月与治疗前比较肌酸激酶值明显下降、肌力评分明显增高(均P < 0.001);移植组治疗后各时间点肌酸激酶值较常规治疗组低、肌力评分较常规治疗组高(均P < 0.001)。②脐血间充质干细胞移植治疗能明显改善肺部影像学异常,且安全性好。③移植治疗后6个月干扰素γ水平显著升高,而白细胞介素4水平显著下降(均P < 0.01);移植治疗后 3,6 个月白细胞介素17水平显著下降(均P < 0.01)。④移植治疗后6个月白细胞介素4、白细胞介素17水平与肌酸激酶水平成正相关(r=0.467和0.488,均P < 0.05);干扰素γ水平与肌酸激酶水平无明显相关(r=0.213,P > 0.05)。结果表明给予糖皮质激素及免疫抑制剂治疗同时,联合脐血间充质干细胞移植治疗多发性肌炎/皮肌炎安全、有效,可调节多发性肌炎/皮肌炎患者免疫网络效应、改善免疫耐受。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

肿瘤坏死因子α预处理脐血间充质干细胞移植治疗心肌梗死

文章快速阅读：文题释义： 心肌缺血：是指心脏的血液灌注减少,导致心脏的供氧减少,心肌能量代谢不正常,不能支持心脏正常工作的一种病理状态。血压降低、主动脉供血减少、冠状动脉阻塞,可直接导致心脏供血减少;心瓣膜病、血黏度变化、心肌本身病变也会使心脏供血减少,心肌缺血对心脏和全身可能带来许多危害。目前针对这种疾病治疗主要的作用机制包括：降低心肌耗氧量,提高耐缺氧能力,清除自由基、抗氧化作用,调节血栓素A 2/前列环素,调节一氧化氮细胞内皮素1、抑制肿瘤坏死因子α和白细胞介素的释放等。 脐血间充质干细胞移植：移植成功最主要的障碍为移植后只有少量脐血间充质干细胞移植至心肌内并存活,因此提高脐血间充质干细胞向心肌内迁移和定植及其存活率对治疗效果具有重要意义。移植前对脐血间充质干细胞进行肿瘤坏死因子α预处理,发现肿瘤坏死因子α预处理胎儿脐血间充质干细胞移植治疗大白兔缺血性心脏病可以改善心脏功能、减少心肌梗死面积和心肌纤维化面积。 摘要 背景：心肌缺血损伤后,心肌细胞释放大量炎症递质作为对心肌损伤的应答,梗死及缺血区的炎症因子有助于心肌组织对损伤的修复和适应。 目的：探讨肿瘤坏死因子α预处理脐血间充质干细胞移植治疗对心肌梗死兔心功能的效果。 方法：将36只大白兔随机等分为4组,假手术组、模型组、无肿瘤坏死因子α组和肿瘤坏死因子α组,后3组建立心肌梗死模型。造模后24 h,模型组、无肿瘤坏死因子α组和肿瘤坏死因子α组分别在梗死中心区及边缘注射PBS、未经肿瘤坏死因子α预处理的脐血间充质干细胞及经肿瘤坏死因子α预处理的脐血间充质干细胞。 结果与结论：与模型组相比,肿瘤坏死因子α组和无肿瘤坏死因子α组兔心脏功能明显恢复,心肌梗死面积及心肌纤维化面积明显减小;且肿瘤坏死因子α组的效果优于无肿瘤坏死因子α组。表明肿瘤坏死因子α预处理胎儿脐血间充质干细胞移植能有效治疗心肌梗死。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程 ORCID: 0000-0002-4513-3726(王巍)     

移植不同剂量脐带间充质干细胞提高老年痴呆大鼠学习记忆能力的比较

BACKGROUND:To delay the onset of Alzheimer’s disease, transplantation of viable and well-differentiated stem cells is expected to repair neural tissue, which has been an issue of concern. OBJECTIVE:To explore the effects of different doses of human umbilical cord mesenchymal stem cells (hUCMSCs) on learning and memory ability of Alzheimer’s disease rats. METHODS:Fifty Sprague-Dawley rats, 7 months of age, were randomized into normal, model, high-, middle- and low-dose hUCMSCs groups (n=10 per group). Rats in model and UCMSCs groups were used to make Alzheimer’s disease animals through intraperitoneal injection of 150 mg/kg D-galactose for 90 days, and rats in the normal group were given intraperitoneal injection of normal saline for 90 days. In the three hUCMSCs group, passage 3 hUCMSCs at doses of 1×10⁵/0.2 mL/20 g, 5×10⁵/0.2 mL/20 g, and 1×10⁶/0.2 mL/20 g were injected via the tail vein, respectively. Forty-five days after cell transplantation, Morris water maze test was used to detect rat’s learning and memory abilities, and hematoxylin-eosin staining was used to observe pathological changes of the rat hippocampal CA1 region. RESULTS AND CONCLUSION:Compared with the normal group, the rats in the model group showed significant reduction in the ability of learning and memory. Compared with the model group, the escape latency was significantly shortened in the middle-dose hUCMSCs group (P < 0.05), while the number of passing times through the platform was increased significantly (P < 0.05). In the model group, the cells in the hippocampal CA1 region were arranged irregularly with unclear nucleoli and a part of cells were concentrated and deeply stained. In the middle-dose hUCMSCs group, the cells in the hippocampal CA1 region were arranged regularly with clear nucleoli, and only individual cells were stained deeply. These findings indicate that middle-dose hUCMSCs transplantation can improve the learning and memory abilities of Alzheimer’s rats.     

Fate of transplanted bone marrow derived mesenchymal stem cells following spinal cord injury in rats by transplantation routes

This research was performed to investigate the differences of the transplanted cells' survival and differentiation, and its efficacy according to the delivery routes following spinal cord injury. Allogenic mesenchymal stem cells (MSCs) were transplanted intravenously (IV group) or intralesionally (IL group) at post-injury 1 day in rats. Behavioral improvement, engraftment and differentiation of the transplanted cells and the expression of neurotrophic factors of the transplanted groups were analyzed and compared with those of the control group. At 6 weeks post-injury, the mean BBB motor scales in the control, IV and IL groups were 6.5 ± 1.8, 11.1 ± 2.1, and 8.5 ± 2.8, respectively. Regardless of the delivery route, the MSCs transplantation following spinal cord injuries presented better behavioral improvement. The differentiations of the engrafted cells were different according to the delivery routes. The engrafted cells predominantly differentiated into astrocytes in the IV group and on the other hand, engrafted cells of the IL group demonstrated relatively even neural and glial differentiation. The expressions of neuronal growth factor were significantly higher in the IL group (mean relative optical density, 2.4 ± 0.15) than those in the control (2.16 ± 0.04) or IV group (1.7 ± 0.23). Transplantation of MSCs in the early stage of spinal cord injury gives a significant clinical improvement. However, the fate of the transplanted MSCs and expression of neuronal growth factors are different along the transplantation route.     

脐血间充质干细胞移植对心肌细胞凋亡的影响

BACKGROUND: Umbilical cord blood mesenchymal stem cell transplantation can reduce myocardial apoptosis and myocardial fibrosis, thereby improving the cardiac function.     

脐血干细胞移植及电针治疗脊髓损伤大鼠神经生长因子及神经营养因子3的表达

背景：研究表明,脐血干细胞移植对脊髓损伤的恢复起促进作用,而电针也能够通过抑制星形胶质细胞增生,来减少损伤部瘢痕形成,故推测两者结合可能在急性脊髓损伤治疗中发挥重要作用。 目的：观察人脐血干细胞局部移植联合督脉电针治疗后大鼠脊髓损伤组织神经生长因子、神经营养因子3的表达。 方法：选取雌性SD大鼠72只,随机分为对照组、损伤组、移植组、联合组。对照组单纯性背部切口后缝合,损伤组脊髓横断处(T₁₀水平)放置约1 mm×2 mm×2 mm大小、浸润生理盐水的明胶海绵;移植组及联合组在脊髓横断处放置浸润人脐血干细胞悬液的明胶海绵,联合组于造模后1 h开始给予督脉电针治疗。在相应处理7,14,28 d后应用免疫组织化学、Western Blot及实时荧光定量PCR方法检测脊髓组织神经生长因子、神经营养因子3表达量的变化。 结果与结论：脊髓损伤后,移植组与损伤组相比,联合组与移植组相比,神经生长因子、神经营养因子3在7,14,28 d表达量均增加(P < 0.05)。Western Blot、实时荧光定量PCR与免疫组化结果相一致。结果显示人脐血干细胞移植与电针联合治疗脊髓损伤具有协同作用,显著上调损伤脊髓神经生长因子、神经营养因子3的表达水平,有利于脊髓损伤后功能恢复。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

脐血造血干/祖细胞移植SCID小鼠的实验研究

目的 :检测扩增后脐血造血干 祖细胞的体内移植能力和造血活性 ,建立脐血细胞体外扩增优化方案和体内移植的SCID小鼠模型。方法 :采用无基质接触的液体悬浮培养方法扩增脐血CD34 细胞 ,将扩增前后的细胞移植给预先经过亚致死量辐照的SCID小鼠 ,4w后通过免疫荧光标记、PCR等检测存活小鼠体内的人源细胞。结果 :连续培养一定时间后 ,FL TPO SCF IL 6组脐血细胞得到持续扩增 ,并能维持一定比例的CD34 细胞 ;SCF IL 3 IL 6 GM CSF EPO组在第 2周时集落形成数已降低 ,第 4周时集落形成的细胞、CD34 细胞已基本检测不到。移植至少 4w后 ,在存活小鼠体内检测到人CD4 5 细胞和Alu基因。结论 :因子组合FL TPO CSF IL 6可以有效扩增脐血CD34 细胞 ,而且扩增后的细胞具有较高的移植效率和造血活性     

脐血间充质干细胞移植治疗帕金森病的可行性

背景：研究证实干细胞在体内体外均可被诱导分化成多巴胺能神经元,这为干细胞移植治疗帕金森病提供了理论基础。 目的：探讨脑内移植脐血间充质干细胞治疗帕金森病模型大鼠的可行性及作用机制。 方法：SD大鼠脑内注射6-羟基多巴建立帕金森病模型,将22只造模成功大鼠随机分为脐血间充质干细胞移植组12只和对照组10只,脑内分别注射脐血间充质干细胞悬液和磷酸盐缓冲液。细胞移植后第1-8周,每周腹内注射阿朴吗啡观察大鼠旋转行为,并于第2,8周取大鼠纹状体和黑质部分行免疫组织化学染色。 结果与结论：①脐血间充质干细胞移植组大鼠转圈次数随着时间延长逐渐下降,而对照组大鼠转圈次数没有明显改变,且移植后3-8周两组旋转圈数差异有显著性意义(P < 0.05)。②移植后2周时,脐血间充质干细胞移植组大鼠纹状体针道内及附近有酪氨酸羟化酶阳性细胞存在;对照组大鼠的纹状体针道处无外源性细胞存在。移植后8周时,脐血间充质干细胞移植组鼠纹状体针道内仍有细胞存活,并有酪氨酸羟化酶阳性细胞存在,对照组大鼠纹状体处无酪氨酸羟化酶阳性细胞表达。结果表明脐血间充质干细胞移植后可在脑内存活并且表达酪氨酸羟化酶蛋白,且能改善帕金森病模型大鼠的行为学异常。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

人脐血间充质干细胞移植联合神经节苷脂注射治疗脑性瘫痪

BACKGROUND:In recent years, some studies have demonstrated that ganglioside can promote survival and differentiation of umbilical blood cord mesenchymal stem cells in vitro. OBJECTIVE:To observe the effect of injection of human umbilical blood cord mesenchymal stem cells and ganglioside into rat lateral ventricles on neurological functional recovery from cerebral palsy. METHODS:Totally 60 cerebral palsy neonatal rats were delivered from pregnant rats which were modes were given intraperitoneal injection of lipopolysaccharide for 2 successive days on day 17 of gestation. Then those neonatal rats were randomly divided into five groups, including model group (n=10), sham transplantation group (n=10), stem cell transplantation group (n=18), ganglioside group (n=10) and combination group (n=12). Under stereotaxic instrument, umbilical blood cord mesenchymal stem cells or ganglioside were injected into left lateral ventricles of the rat brain, respectively, and the sham transplantation group was given the same volume of phosphate buffered saline. Two rats from the stem cell transplantation group were put to death for immunofluorescence staining at 7, 14, 21 and 28 days after transplantation, respectively, and two rats in the combination group were killed for immunofluorescence staining at 14 days. Besides, all rats were underwent neurologic evaluation at 28 days after transplantation. RESULTS AND CONCLUSION:The umbilical blood cord mesenchymal stem cells could survive, migrate and differentiate, which mainly distributed in the lateral ventricle, hippocampus and cortex. At 14 days after transplantation, positive expressions of BrdU and glial fibrillary acidic protein in the combination group were significantly higher than those in the stem cell transplantation group (P < 0.05). In addition, compared with the model group, the holding time significantly prolonged and foot error times significantly decreased in the latter three groups (P < 0.05), as well as in the combination group compared with the stem cell transplantation and ganglioside groups (P < 0.05). These results indicate that umbilical blood cord mesenchymal stem cells and ganglioside can both improve neurological function of rats with cerebral palsy. Given that ganglioside can promote survival and differentiation of umbilical blood cord mesenchymal stem cells in vivo, the combined transplantation is preferred.     

舒芬太尼复合丙泊酚全身麻醉在脐血间充质干细胞移植治疗脊髓损伤中的应用

BACKGROUND:Sufentanil and propofol are both found to have good neuroprotective effects on neurological damage in clinical practice. OBJECTIVE:To investigate the effect of propofol combined with sufentanil in umbilical cord blood mesenchymal stem cells transplantation for the treatment of spinal cord injury. METHODS:Sixty-five Wistar rats were selected to make animal models of acute spinal cord injury using Allen’s method. Six hours after modeling, these rats were randomly assigned into combined group (injection of 2×10⁷/L human umbilical cord blood mesenchymal stem cell suspension (0.5 mL) plus injection of 1.0-1.5 mg/kg propofol and 0.5 μg/kg sufentanil via the tail vein), stem cell group (injection of 2×10⁷/L human umbilical cord blood mesenchymal stem cell suspension (0.5 mL) via the tail vein), or control group (injection of 30 μL of LDMEM containing 5% fetal bovine serum). S100β protein level in serum was detected in each group at 15 and 60 minutes after injection. Motor function of rat in each group was assessed by Basso Beattie Bresnahan (BBB) scoring and incline plane test at 1, 2, 4, 6, 8 weeks after modeling. Pathological changes of the spinal cord were observed at 4 weeks after modeling. Expression of vascular endothelial growth factor was detected using western blot assay at 1 and 2 weeks after modeling. RESULTS AND CONCLUSION:After 15 and 60 minutes of intervention, S100β protein level was lowest in the combined group followed by the stem cell and control groups (P < 0.05). At 2, 4, 6, 8 weeks after modeling, scores on the incline plane test and BBB were ranked as follows: combined group > stem cell group > model group (P < 0.05). At 4 weeks after modeling, severe damage to the spinal cord and few nerve fibers were found in the control group; spinal cord hyperplasia and a few of regenerated axons and PKH-26-positive stem cells appeared in the stem cell group; while in the combined group, there were a large amount of PKH-26-positive stem cells and nerve axon-like structures. At 1 and 2 weeks after modeling, the highest protein level of vascular endothelial growth factor was found in the combined group followed by the stem cell group and control group (P < 0.05). To conclude, these findings indicate that propofol and sufentanil in umbilical cord blood mesenchymal stem cell transplantation therapy can promote the recovery of hindlimb function after spinal cord injury, thereby promoting the functional recovery of rats from spinal cord injury.     

胎盘间充质干细胞的应用研究

背景：胎盘间充质干细胞因其具有来源广泛、免疫原性低、不涉及伦理问题等优点成为种子细胞的新来源。 目的：阐述胎盘间充质干细胞的来源、生物学特性及应用最新研究进展。 方法：检索 PubMed、ScienceDirect、OvidSP、CNKI 数据库相关文章,检索时限为2003至 2015年,英文检索词为“Placenta,Mesenchymal stem cells,The placenta mesenchymal stem cells, Cell transplantation , Application mechanism”,中文检索词为“胎盘,间充质干细胞,胎盘间充质干细胞,细胞移植,应用机制”,从中筛选出与主题相关且论据可靠的部分文献,最终纳入57篇文章进行归纳综述。 结果与结论：目前已成功分离培养出胎盘间充质干细胞,并对其生物学特性进行研究,证明其具有干细胞源性及多向分化潜能。目前有较多关于胎盘间充质干细胞应用于实验动物及临床的研究,在骨组织工程、血管再生及神经组织等修复过程中均显示出了巨大的潜力,但胎盘间充质干细胞的具体应用机制目前尚不清楚,尚处于探索阶段,在胎盘间充质干细胞广泛应用于临床之前,仍有许多问题有待进一步研究明确,以确保其安全性和有效性。  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

舒芬太尼联合脐血间充质干细胞移植对梗死心肌的保护作用

背景:药物预处理的延迟性保护作用成为近年来预处理领域的研究热点,舒芬太尼是一种非选择性阿片受体激动剂,有明显的心肌保护作用。目的:探讨舒芬太尼预处理联合脐血间充质干细胞移植对心肌梗死后损伤心肌的保护作用。方法:采用结扎左冠状动脉前降支的方式建立大鼠心肌缺血再灌注模型(缺血30 min,再灌注180 min),建模后随机分为缺血再灌注组,脐血间充质干细胞组,舒芬太尼+脐血间充质干细胞组,每组30只。缺血再灌注组于缺血再灌注前5 min经腹腔静脉注射1 mL生理盐水,脐血间充质干细胞组经腹腔静脉注射脐血间充质干细胞悬液1 m L,舒芬太尼+脐血间充质干细胞组在此基础上于冠脉阻断前10 min经腹腔静脉注射舒芬太尼10μg/kg,治疗后2周进行相关指标检测。结果与结论:(1)心肌梗死面积:舒芬太尼+脐血间充质干细胞组<脐血间充质干细胞组<缺血再灌注组,差异有显著性意义(P<0.05);(2)与缺血再灌注组比较,脐血间充质干细胞组血清肌酸激酶、乳酸脱氢酶及肌钙蛋白Ⅰ水平降低,一氧化氮水平增加,与脐血间充质干细胞组比较,舒芬太尼+脐血间充质干细胞组血清肌酸激酶、乳酸脱氢酶及肌钙蛋白I水平明显降低,一氧化氮水平增加更明显,差异有显著性意义(P<0.05);(3)Caspase-3蛋白表达:舒芬太尼+脐血间充质干细胞组<脐血间充质干细胞组<缺血再灌注组,差异有显著性意义(P<0.05);(4)血流动力学指标:与缺血再灌注组比较,脐血间充质干细胞组、舒芬太尼+脐血间充质干细胞组左心室舒张压升高,左心室舒张末压降低,差异有显著性意义(P<0.05);(5)与缺血再灌注组比较,脐血间充质干细胞组心肌组织病理学损伤程度减轻,舒芬太尼+脐血间充质干细胞组明显减轻;(6)结果表明,舒芬太尼预处理联合脐血间充质干细胞移植能够减轻大鼠心肌梗死程度,保护损伤的心肌。