8-溴-7-甲氧基白杨素和索拉非尼对肝癌干细胞样细胞凋亡的影响

背景：拟尝试结合8-溴-7-甲氧基白杨素和索拉非尼的优点扬长避短,弥补肝细胞癌肿瘤干细胞对索拉非尼的耐药,综合提高肝细胞癌的治疗效果。 目的：观察8-溴-7-甲氧基白杨素和索拉非尼单用及二者联用对体外培养的SMMC-7721细胞系肝癌干细胞样细胞凋亡的影响,并分析其作用机制。 方法：8-溴-7-甲氧基白杨素、索拉非尼单用作为对照组,二者合用作为实验组,分别作用于SMMC-7721细胞系球形细胞24 h,流式细胞术检测细胞凋亡情况,Western blot分析NF-κB(p65)蛋白表达水平。 结果与结论：与8-溴-7-甲氧基白杨素单用和不同浓度索拉非尼单用对照组比较,8-溴-7-甲氧基白杨素与索拉非尼(2.5,5,10,50 μmol/L)二者合用实验组明显提高了SMMC-7721细胞系球形细胞的凋亡率,且明显下调了NF-κB(p65)蛋白的表达。结果表明8-溴-7-甲氧基白杨素可增强索拉非尼对肝癌干细胞样细胞凋亡的诱导作用,作用机制与NF-κB(p65)蛋白表达下调可能相关。 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     

5-氮胞苷诱导兔脂肪干细胞分化为心肌样细胞的特定基因表达

背景：采用生物学技术将脂肪干细胞进行心肌内移植,修复损伤心肌组织是近年来心血管病研究领域的一大热点。脂肪干细胞经诱导分化后的特定心肌基因表达尚无全面的研究报道。 目的：观察兔脂肪干细胞经5-氮胞苷诱导分化为心肌样细胞后心肌特异性基因的表达。 方法：取第2代脂肪干细胞,加入2.5,5,10,20,40,80 μmol/L 5-氮胞苷经24 h作用后,用完全培养液对其继续进行培养,4周后再观察细胞生长和形态学的改变。待诱导1,2,3,4周,利用RT-PCR技术检测心钠素,脑钠素,α-骨骼肌动蛋白的基因表达。 结果与结论：5-氮胞苷诱导1周,其细胞大多呈紧密平行排列,其体积有所增大,梭形细胞比例相对有所下降,40,80 μmol/L组细胞形态变化明显。诱导第4周时,40,80 μmol/L组细胞折光性减弱,细胞活性减弱,细胞死亡数继续增加。RT-PCR检测心钠素,脑钠素,α-骨骼肌动蛋白的基因表达呈逐渐增加趋势;10 μmol/L组各基因的表达明显高于其他各组(P < 0.05)。结果提示兔脂肪干细胞经5-氮胞苷诱导分化的细胞具有心肌细胞的某些基因的特异性表达。     

多聚赖氨酸修饰γ-Fe2O3纳米颗粒标记不影响神经母细胞瘤干细胞的活化和增殖

BACKGROUND: Retinoic acid is the most promising inducer for neuroblastoma minimal residual lesion, and it can induce cell differentiation in vivo, accompanied by reducing tumor cell proliferation. OBJECTIVE: To study the effect of nanoparticle labeling on biological characteristics of neuroblastoma stem cells, and the role of 13-cis retinoic acid to induce differentiation of neuroblastoma stem cells. METHODS: Neuroblastoma stem cells were isolated and cultured in vitro using serum-free suspension culture method, labeled with polylysine-modified γ-Fe2O3 nanoparticles and induced in culture medium containing 13-cis retinoic acid. RT-PCR was used to detect the expression of Oct-4 before and after labeling as well as before and after induction. Immunofluorescence method was used to detect the expression of nestin before and after labeling as well as before and after induction. RESULTS AND CONCLUSION: Neuroblastoma stem cells were successfully cultured in the bone marrow samples from 5 of 20 cases. Polylysine-modified γ-Fe2O3 nanoparticle labeling did no influence the viability and proliferation ability of neuroblastoma stem cells, and also had no effect on Oct-4 mRNA and nestin expression. After cultured in the culture medium containing 13-cis retinoic acid, the cell shape changed and the growth rate slowed down. Moreover, the expression of Oct-4 mRNA and nestin was gradually reduced. These findings indicate that polylysine-modified gamma-Fe2O3 nanoparticles can be used to label neuroblastoma stem cells, and 13-cis retinoic acid can induce the differentiation of neuroblastoma stem cells.      

缺氧和无血清培养对骨髓间充质干细胞内源性硫化氢生成的影响

背景：大鼠骨髓间充干细胞移植后的低存活率多与缺血微环境相关,而硫化氢可以对抗多种细胞与组织的凋亡和损伤模型。 目的：检测大鼠骨髓间充质干细胞在不同缺氧和无血清培养时间后的细胞凋亡、细胞活力、硫化氢含量及其合成酶体系的变化情况。 方法：取第3代大鼠骨髓间充质干细胞,设立5个(0,3,6,12和24 h)不同的缺氧和无血清培养时间点。用SubG1法检测细胞的凋亡率,用CCK-8法检测细胞的活力,并检测细胞培养基中硫化氢的含量以及细胞中硫化氢合成酶体系的表达变化情况。 结果与结论：与正常培养组相比,缺氧和无血清培养不同时间后,细胞的凋亡率显著增高,细胞活力明显下降。缺氧和无血清时间越长,细胞凋亡越多,活力越低,并且细胞培养基中硫化氢含量和细胞中硫化氢合成酶体系的表达也越低,差异有显著性意义。表明缺氧和无血清培养可以抑制大鼠骨髓间充质干细胞中硫化氢及其合成酶体系的生成和表达。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：     

干细胞诱导分化为毛囊及再生的研究进展

BACKGROUND:Stem cells have the potential to differentiate into various organs and tissues. In recent years, stem cells have been proved to differentiate into hair follicles under certain conditions. OBJECTIVE:To review the research progress and prospect of stem cells differentiating to hair follicles, thereby providing a reliable basis for clinical treatment of serious hair follicle injury. METHODS:A computer-based search of PubMed, EMBASE, WanFang, CNKI databases was performed for related articles published between 2013 and 2015, using the keywords of “cell hair, follicle stem, medicine regenerative, differentiation” in English and Chinese. A total of 207 articles were retrieved, and finally 34 articles were included in result analysis. RESULTS AND CONCLUSION:Stem cells from different sources all have the ability to differentiate into hair follicles under certain inductions. However, it is important to seek more scientific and rational methods for the differentiation of stem cells into hair follicles based on overcoming their own shortcomings. A great progress has been made in animal experiments and subclinical trials, and even a great breakthrough in some aspects. Further studies on combining the advantages and overcoming the shortcomings of various stem cells during differentiation are required for the clinical treatment of serious hair follicle injury.     

衰老可导致间充质干细胞氧化损伤修复能力降低

背景：DNA损伤及损伤后的应答异常会导致基因组不稳定,基因组不稳定是肿瘤形成的重要因素之一。在细胞衰老过程中,衰老细胞基因组稳定性下降,对于端粒、端粒酶的研究以及对于原癌基因和抑癌基因的研究,表明细胞衰老和肿瘤有密切的联系。 目的：以氧化损伤为模型,探索DNA损伤应答异常是衰老细胞基因组不稳定性的直接原因。 方法：培养骨髓间充质干细胞,流式细胞术进行检测鉴定。衰老相关β-半乳糖苷酶检测细胞衰老情况,BrdU掺入实验检测细胞增殖情况。建立体外培养人间充质干细胞衰老模型,通过CCK-8法检测细胞存活情况, DCFH-DA荧光探针检测细胞内活性氧,单细胞凝胶电泳观察细胞DNA损伤情况。 结果与结论：人间充质干细胞经长期培养发生衰老,培养40代以后,衰老相关β-半乳糖苷酶染色阳性细胞明显增多,BrdU掺入能力显著下降,提示间充质干细胞长期培养后发生衰老。生存曲线结果显示H₂O₂作用下,年轻间充质干细胞存活率明显高于衰老间充质干细胞;活性氧及单细胞凝胶电泳结果显示,H₂O₂处理后衰老间充质干细胞DNA损伤更严重,修复时间更长,说明衰老间充质干细胞比年轻间充质干细胞对H₂O₂损伤更为敏感。     

骨髓间充质干细胞移植联合氯化锂治疗兔股骨头缺血坏死疗效

BACKGROUND: Lithium chloride can promote the proliferation and osteogenic capacity of bone marrow mesenchymal stem cells in the necrotic region after avascular necrosis of the femoral head, which has become an issue of concern. OBJECTIVE: To compare the advantages and disadvantages of bone marrow stem cell transplantation combined with lithium chloride in the treatment of rabbit femoral head necrosis. METHODS: Passage 2 bone marrow mesenchymal stem cells from 1-week-old New Zealand rabbits were cultured in 0, 5, 10, 20, 40 mmol/L lithium chloride. Forty-eight healthy adult New Zealand rabbits were selected to make femoral head necrosis models in the right femoral head using liquid nitrogen freezing method and then randomized into four groups: model group with no implantation; lithium chloride group given lithium chloride treatment at 3 days after modeling; cell transplantation group given gelatin sponge implantation and bone marrow mesenchymal stem cell suspension injection into the femoral head after modeling; combined group given bone marrow mesenchymal stem cell suspension injection and lithium chloride treatment. Intraperitoneal injection of lithium chloride (45.2 mg/kg) was given daily beginning at the postoperative 3rd day, and the treatment duration was 4 weeks. RESULTS AND CONCLUSION: Lithium chloride at 10 mmol/L had the maximum effect on the proliferation of rabbit bone marrow mesenchymal stem cells, and if the concentration of lithium chloride was > 10 mmol/L, the promotion role of lithium chloride began to decline. After combined treatment, the morphology of the femoral head was restored a little, with increased bone density and thickened trabecular bone; the level of β-catenin in the femoral head was significantly increased in the combined group compared with the cell transplantation group or the lithium chloride group. These findings show that bone marrow stem cell transplantation combined with lithium chloride treatment can promote the recovery from femoral head necrosis by increasing bone mass of the trabecular bone and bone density of the femoral head in the necrotic region.      

人诱导性多能干细胞源神经元移植治疗帕金森病的现状与未来

BACKGROUND:The emergence of human induced pluripotent stem cells (iPSCs)-derived dopaminergic neurons solves the problem that the embryonic stem cell (ESC) shows an ethical issue on its source, providing a promising cell source for treatment of Parkinson’s disease. OBJECTIVE:To summarize the differentiation methods of iPSCs-derived dopaminergic neurons in vitro, the choice of Parkinson’s disease models and the transplantation of iPSCs-derived dopaminergic neurons in the Parkinson’s disease treatment. METHODS: In order to search relevant articles about the application of iPSCs-derived dopaminergic neurons in the Parkinson’s disease models from PubMed databases (from 1980 to 2015), a computer-based search was performed by the first author, using the key words of “iPSC and Parkinson’s disease, induced pluripotent stem cells and Parkinson’s disease, ES cells and Parkinson, PD model, Parkinson and Lewy bodies” in English. Finally 40 articles were chosen for further analysis. RESULTS AND CONCLUSION:Here, this paper is detailed to show the research status of human iPSCs-derived dopaminergic neurons for treating Parkinson’s disease by reviewing the sources and in vitro differentiation schedules of iPSCs as well as the choice of Parkinson’s disease models and outcomes of transplantation of iPSCs-derived dopaminergic neurons for Parkinson’s disease treatment. According to the Parkinson’s disease mechanism of the Lewy body, we analyze the generation mechanism of the Lewy body, providing references to avert the presence of Lewy bodies and optimize the outcomes of transplantation. The improvement of differentiation conditions of iPSCs can markedly improve the behavior outcomes, and moreover, we can systematically evaluate the outcomes of transplantation by iconography and immunohistochemical results.     

去胰岛素的乳腺癌干细胞培养及雌激素诱导的作用

 目的：探讨去除胰岛素的乳腺癌干细胞悬浮培养方法以及雌激素诱导的作用。方法：通过使用去除胰岛素的悬浮培养方法获得乳腺癌细胞系MCF7的肿瘤球细胞,并通过形态学观察、CD24-CD44+表达细胞的检测、醛脱氢酶1（ALDH1）蛋白的表达以及细胞多向分化能力对该干细胞模型的可靠性进行鉴定。给予10-10 mol/L 17β-雌二醇(E2β)对该干细胞模型处理7 d,观察上述相关指标的变化。结果：去除胰岛素的悬浮培养方法获得的瘤细胞球呈葡萄状,由30～60个细胞组成。细胞球显示细胞角蛋白18和CD10蛋白均表达阳性,CD44+CD24-细胞的含量及ALDH1蛋白表达量均较贴壁细胞明显增高（P<0.05）。使用10-10 mol/L E2β处理MCF7肿瘤球细胞7 d,肿瘤球细胞数及体积增大。使用10-10 mol/L E2β处理MCF7肿瘤球细胞24 h,CD44+CD24-细胞数量及ALDH1蛋白表达量较未处理组明显升高（P<0.05）。结论：去除胰岛素的悬浮培养方法可有效建立乳腺癌干细胞体外研究模型,并可用于E2β对乳腺癌干细胞生长调控的研究。     

定向诱导分化环境下骨髓间充质干细胞向成骨及成脂细胞的分化

背景：骨髓间充质干细胞属于骨髓中的非造血干细胞,能够在不同的条件下诱导分化为软骨细胞、骨细胞以及脂肪细胞等,是最有前途的组织工程种子细胞。 目的：探讨定向诱导分化环境下骨髓间充质干细胞向成骨细胞及脂肪细胞分化的关系。 方法：无菌抽取日本大耳兔骨髓,采用密度梯度离心法和细胞贴壁法分离、纯化出骨髓间充质干细胞,分别采用成脂诱导培养基和成骨诱导培养基进行诱导培养,培养后不同时间点进行苏丹Ⅳ染色、Von Kossa染色、碱性磷酸酶活性检测,比较细胞成脂和成骨率。以正常DMEM培养液培养细胞为对照组。 结果与结论：骨髓间充质干细胞经过7 d成脂诱导后细胞浆开始出现小脂滴、细胞无序,培养21 d后细胞浆内形成高折光性的脂滴。苏丹Ⅳ染色结果显示：骨髓间充质干细胞克隆中心的细胞浆内存在大量的颗粒状红色脂滴,对照组仅5%骨髓间充质干细胞分化为脂肪细胞。骨髓间充质干细胞经过7 d成骨诱导后细胞逐渐汇合成铺路石状,并且形成多个结节;培养14 d后能够看见褐色点状矿化结节中心;培养21 d后形成小片状矿化结节。成骨诱导实验组成骨率为40%,成脂率为20%,显著高于对照组(成骨率为5%,成脂率为5%)。结果提示在适当的环境下骨髓间充质干细胞能够一部分转化为脂肪细胞,另一部转化为骨细胞,并且二者存在一定的联系,即分化的脂肪细胞多,骨细胞则少;反之分化的脂肪细胞少,骨细胞则多。  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     

移植骨髓间充质干细胞肝癌大鼠细胞凋亡及炎症因子的动态变化

BACKGROUND:Bone marrow mesenchymal stem cell transplantation has not been thoroughly reported on its effects on apoptosis in hepatoma carcinoma cells and inflammatory factor level. OBJECTIVE:To investigate the effect of rat bone marrow mesenchymal stem cells on dynamic change of inflammatory factors and cell apoptosis during hepatocarcinogenesis. METHODS:Sixty healthy Sprague-Dawley rats were divided randomly into healthy group (n=30), control group (n=30) and transplantation group (n=30). Healthy group was given ordinary feed and normal water, while other groups were given diethylnitrosamine solution in drinking water to induce liver cancer models. Then, rats in the transplantation group were subjected to bone marrow mesenchymal stem cell transplantation via the tail vein. Two weeks after cell transplantation, CXCL5, interleukin-8 and interleukin-6 levels were tested by ELISA, mRNA level of hepatocyte nuclear factor 1α detected by RT-PCR, expression of Bcl-2 and Bax in liver tissue measured by immunohistochemical method, and liver cancer cell apoptosis index detected by TUNEL technique. RESULTS AND CONCLUSION:After modeling, the expressions of CXCL5, interleukin-8 and interleukin-6 in the control group were significantly higher than those in the healthy group (P < 0.05), while these indexes were reduced significantly after bone marrow mesenchymal stem cell transplantation (P < 0.05) and close to the normal levels (P > 0.05). Bone marrow mesenchymal stem cell transplantation significantly up-regulated the mRNA level of hepatocyte nuclear factor 1α in the liver tissue that was decreased obviously after modeling (P < 0.05). In addition, the expression of Bcl-2 was reduced, while the expression of Bax and the apoptosis index increased significantly in the transplantation group compared with the control group (P < 0.05). These findings indicate that bone marrow mesenchymal stem cell transplantation contributes to hepatocyte differentiation and regeneration in liver cancer rats by reducing serum inflammatory factor levels and promoting apoptosis in hepatoma carcinoma cells.     

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.     

葛根芩连汤联合人羊膜间充质干细胞移植治疗糖尿病早期视网膜病变

BACKGROUND:Human amniotic mesenchymal stem cells have the potential to differentiate into insulin-secreting cells and have immunomodulatory effects. Additionally, it has been clinically proved that Gegen Qin Lian Tang can lower blood sugar. OBJECTIVE:To investigate the effects of Gegen Qin Lian Tang combined with human amniotic mesenchymal stem cell transplantation on rat early diabetic retinopathy, by detecting pathological changes, levels of blood indicators and expressions of vascular endothelial growth factor in retinal tissues. METHODS:By intraperitoneal injection of streptozotocin, 42 Wistar rat models with diabetes mellitus were prepared and then randomly divided into model group, human amniotic mesenchymal stem cell transplantation group (cell transplantation group) and combination of human amniotic mesenchymal stem cells and Gegen Qin Lian Tang group (combination group). At 4 weeks after transplantation, levels of blood sugar and serum insulin in diabetic rats were detected; pathological changes of the retina in diabetic rats were observed by hematoxylin-eosin staining. Besides, expressions of CD45 and vascular endothelial growth factor mRNA were detected using immunohistochemistry staining and RT-PCR technology, respectively. RESULTS AND CONCLUSION:Compared with the model group, the levels of blood glucose and serum insulin in both cell transplantation and combination groups were significantly decreased and increased, respectively, and these changes were even more significant in the combination group (P < 0.05). In the model group, the retinal edema could be found, accompanied by structural disorder and irregular cell arrangement, while these retinal lesions were relatively milder in the cell transplantation group and significantly improved in the combination group. In addition, the CD45 expression and in the retina was highest in the model group subsequently followed by the cell transplantation group (P < 0.05) and lowest in the combination group (P < 0.05). Furthermore, compared with the model group, the expression of vascular endothelial growth factor mRNA was also significantly lower in the other two groups, especially in the combination group (P < 0.05). These data show that Gegen Qin Lian Tang combined with human amniotic mesenchymal stem cell transplantation improves the severity of diabetic retinopathy by inhibiting expressions of CD45 and vascular endothelial growth factor in the retinal tissues.     

胎儿脐血间充质干细胞治疗大鼠急性心肌梗死

背景：胎儿脐血间充质干细胞对病变心肌有修复和再生能力,胎儿脐血间充质干细胞移植是治疗心肌梗死的一种新途径。 目的：探讨胎儿脐血间充质干细胞移植治疗大鼠心肌梗死的效果。 方法：选取32只大鼠结扎左冠状动脉前降支制作心肌梗死动物模型,随机等分为移植组和梗死组,从胎儿脐血中分离培养脐血间充质干细胞,制备脐血间充质干细胞悬液,对移植组大鼠进行脐血间充质干细胞移植。 结果与结论：胎儿脐血间充质干细胞在体外可以被成功分离培养;与梗死组相比,移植组大鼠心肌梗死边缘区的微血管密度、左室收缩末压、左室内压最大上升和下降速率显著增加(P < 0.05),左室舒张末压显著下降(P < 0.05),心电图情况稍有好转。表明胎儿脐血间充质干细胞治疗心肌梗死大鼠可以促进心肌血管再生,改善心脏功能。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     

人脐带间充质干细胞腹腔移植治疗急性肝损伤大鼠

背景：体外实验证实人脐带间充质干细胞可诱导成肝样细胞,故认为其可能具有肝脏修复功能。 目的：进行动物体内实验,观察人脐带间充质干细胞移植治疗大鼠急性肝损伤的效果。 方法：将健康SD大鼠随机分为3组,正常对照组不造模,细胞移植组和PBS组腹腔注射体积分数10%CCl4橄榄油溶液制造急性肝损伤模型后24 h,分别经腹腔移植人脐带间充质干细胞悬液0.5 mL和等量PBS。 结果与结论：苏木精-伊红染色显示,CCl4腹腔注射24 h后大鼠肝脏出现急性肝损伤的病理变化,细胞移植后7 d时肝脏结构完全恢复正常,PBS组14 d才恢复正常肝脏组织结构。与正常对照组相比,其他2组大鼠血清丙氨酸转氨酶及天门冬氨酸转氨酶均明显升高(P < 0.05-0.01);人脐带间充质干细胞移植后3 d,大鼠血清2种转氨酶水平较PBS组明显降低(P < 0.05-0.01);7 d后均降至正常水平。移植后第3天肝脏组织内可见抗人核蛋白抗体阳性细胞分布于汇管区,第7天抗人白蛋白抗体的阳性表达。提示经鼠腹腔移植人脐带间充质干细胞后可以在一定程度上改善肝功能及修复受损的肝组织。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：     

脂肪间充质干细胞移植治疗1型糖尿病模型大鼠的作用

背景:干细胞移植是1型糖尿病比较有前景的治疗方法,脂肪间充质干细胞是继骨髓间充质干细胞后的又一研究热点。目的:观察脂肪间充质干细胞移植对1型糖尿病大鼠的治疗作用。方法:将45只SD大鼠随机分为正常组、模型组和细胞移植组,后2组采用链脲菌素腹腔注射建立1型糖尿病模型。造模后7 d,正常组腹腔静脉注射生理盐水,模型组腹腔静脉注射无血清的DMEM培养液,细胞移植组腹腔静脉注射脂肪间充质干细胞悬液。移植后2周,监测各组大鼠体质量、血糖水平,ELISA法检测各组大鼠胰岛素分泌量,RT-PCR检测胰腺组织PDX-1 m RNA的表达。结果与结论:(1)移植前细胞移植组与模型组的体质量均低于正常组,移植后2周细胞移植组大鼠体质量逐渐增加,而模型组的体质量持续下降;(2)与正常组比较,模型组大鼠空腹血糖维持在较高水平(P<0.05),与模型组相比,细胞移植组大鼠空腹血糖水平显著下降(P<0.05);(3)与正常组比较,模型组胰岛素水平明显降低(P<0.05),与模型组比较,细胞移植组胰岛素水平则显著增加(P<0.05);(4)正常组胰腺组织PDX-1 mR NA表达最高,模型组最低,各组间比较差异有显著性意义(P<0.05);(5)结果表明,脂肪间充质干细胞移植促进胰岛组织PDX-1表达,改善了大鼠的高血糖状态。     

脂肪间充质干细胞移植治疗慢性阻塞性肺疾病

BACKGROUND:Chronic obstructive pulmonary disease is progressive respiratory disease characterized by airflow limitation. OBJECTIVE:To investigate the therapeutic effect of adipose-derived mesenchymal stem cell transplantation in rats with chronic obstructive pulmonary disease. METHODS:Sixty healthy male Sprague-Dawley rats were randomly divided into control, model and treatment groups (n=20 per group). Rat models of chronic obstructive pulmonary disease were made in the model and treatment group, while no treatment was done in the control group. After modeling, rats in the treatment group were given tail vein injection of CM-Dil-labeled adipose-derived mesenchymal stem cells, and rats in the model and control groups given the same amount of normal saline. Rat pulmonary ventilation function, inflammatory factor level and pathological changes of the lung were detected at 14 days after cell transplantation. RESULTS AND CONCLUSION:After modeling, reduced lung function was found in rats with chronic obstructive pulmonary disease, but the cell transplantation significantly improved this reduction (P < 0.05). Compared with the model group, significantly reduced indexes were visible in the treatment group (P < 0.05), including the total number of white blood cells, the number of macrophages and neutrophils, levels of interleukin-8, tumor necrosis factor α and C-reactive protein in the bronchoalveolar lavage fluid as well as serum level of malondialdehyde, while serum superoxide dismutase activity was increased significantly in the treatment group (P < 0.05). In the treatment group, emphysema-like changes were mitigated and CM-Dil-labeled adipose-derived mesenchymal stem cells were capable of homing to the lung tissue of rats with chronic obstructive pulmonary disease and survived. All these findings show that adipose-derived mesenchymal stem cell transplantation can improve lung function of rats with chronic obstructive pulmonary disease, and reduce inflammatory response, which has for certain some therapeutic effects.     

人促红细胞生成素基因修饰人羊膜间充质干细胞蛛网膜下腔移植对脑损伤的影响

BACKGROUND:Studies have shown that as a regulator of bone marrow function erythropoietin is a glycoprotein that controls the development of the central nervous system and has neurotrophic and neuroprotective potential. Therefore, transplantation of human amniotic mesenchymal stem cells genetically modified by human erythropoietin is a new choice for brain injury treatment. OBJECTIVE:To observe the effect of transplantation of human amniotic mesenchymal stem cells genetically modified by human erythropoietin on the functional recovery from brain injury in rats. METHODS:Eukaryotic expression plasmid pcDNA3.1 carrying erythropoietin was successfully constructed and transferred into amniotic mesenchymal stem cells cultured in vitro. Expression of erythropoietin was detected using western blot assay before and after transfection. Rat models of middle cerebral arterial occlusion was made and given transplantation of transfected amniotic mesenchymal stem cells via the tail vein (transfection group). Additionally, model and simple cell transplantation groups were set in a comparative study. RESULTS AND CONCLUSION:Findings from western blot detection showed that transfected cells could express human erythropoietin. Compared with the other groups, modified neurologic severity scores, growth-associated protein 43 and aquaporin 9 at mRNA and protein levels were all decreased significantly in the transfection group. Furthermore, the number of cells positive for CM-Dil was highest in the transfection group, followed by simple cell transplantation group, and lowest in the model group (all P < 0.05). Overall findings from this study show that human erythropoietin-modified human amniotic mesenchymal stem cell transplantation promotes neurologic recovery from brain injury through eliciting a reduction in growth-associated protein 43 and aquaporin 9 at mRNA and protein levels as well as inhibiting cell apoptosis.     

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.     

同种异体骨髓间充质干细胞移植在心肌梗死后心室重建中的作用

BACKGROUND:Myocardial infarction leads to ischemic changes in the myocardium, triggering the emergence of ventricular remodeling, which is an important cause of death. Myocardial infarction is a common disease in the middle-aged and elderly population, but autologous bone marrow mesenchymal stem cells from these patients exhibit a weak ability of proliferation and differentiation. Therefore, a positive attempt of allogeneic stem cell transplantation is required in order to obtain better therapeutic outcomes. OBJECTIVE:To explore the effect of allogeneic bone marrow mesenchymal stem cells on ventricular remodeling after myocardial infarction.   METHODS:Bone marrow mesenchymal stem cells from 10 neonatal rats and 10 adult rats were isolated, cultured and identified. Another 40 rats were randomly assigned into four groups (n=10/group): model group, neonatal rat cell transplantation group, adult rat cell transplantation group, or sham group. Animal models of myocardial infarction were made in rats in the all groups except for the sham group in which the rats were given sham operation. Rats in the two cell transplantation groups were given the corresponding cell transplantation. Four weeks postoperatively, heart function of rats was detected in each group, and cardiac tissues were taken to detect changes in collagen formation and blood vessel density in the infarct area. RESULTS AND CONCLUSION:Four weeks after surgery, rats in the model group showed significant changes in cardiac function indexes as compared with the other groups (P < 0.05), while compared with the model group, these cardiac function indexes improved in both two cell transplantation groups, but there was no significant difference between the two cell transplantation groups (P > 0.05). Meanwhile, compared with the model group, significantly decreased collagen formation and increased blood vessel density were found in both two cell transplantation groups (P < 0.05). Additionally, the vascular density of the infarct area was highest in the sham group (P < 0.05). Experimental results show that both neonatal and adult rat bone marrow mesenchymal stem cell transplantation can improve cardiac function of rats, reduce the formation of collagen in the infarct area and delay ventricular remodeling after myocardial infarction.