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1.
Mesenchymal stem cells (MSCs) are plastic-adherent cells with a characteristic surface phenotype and properties of self-renewal, differentiation, and high proliferative potential. The characteristics of MSCs and their tumortropic capability make them an ideal tool for use in cell-based therapies for cancer, including glioma. These cells can function either through a bystander effect or as a delivery system for genes and drugs. MSCs have been demonstrated to inhibit the growth of glioma and to improve survival following transplantation into the brain. We briefly review the current data regarding the use of MSCs in the treatment of glioma and discuss the potential strategies for development of a more specific and effective therapy.  相似文献   

2.
肝细胞移植可用于治疗肝衰竭及多种与肝脏相关的遗传性代谢缺陷疾病.它是实施肝脏导向体外基因治疗的工具,它作为肝移植的替代疗法,越来越受到人们重视,在国外临床试验已取得较理想的治疗效果.国内外肝细胞移植的研究进展可以从肝细胞来源、肝细胞移植方式、移植不良反应等4个方面来综述。  相似文献   

3.
目的:探讨外源性EGFP基因转染修饰兔骨髓间充质干细胞(m esenchymal stem cells,MSCs)的可行性。方法:用增强型荧光绿色蛋白(enhanced green fluorescent protein,EGFP)作为报告基因,以脂质体法转染骨髓间充质干细胞,观察转染结果、表达情况及对靶细胞活力的影响。结果:经荧光显微镜下观察证实:成功地对骨髓间充质干细胞实现了基因转染。结论:兔骨髓间充质干细胞能够在体外适宜的条件下进行长期培养;骨髓间充质干细胞可直接作为基因靶细胞,建立稳定表达EGFP的骨髓间充质干细胞系具有可行性,为进一步做标记的MSCs细胞的移植研究奠定基础。  相似文献   

4.
Orthotopic liver transplantation (OLT) is the only proven effective treatment for both end-stage and metabolic liver diseases. Hepatocyte transplantation is a promising alternative for OLT, but the lack of available donor livers has hampered its clinical application. Hepatocyte-like cells (HLCs) differentiated from many multi-potential stem cells can help repair damaged liver tissue. Yet almost suitable cells currently identified for human use are difficult to harvest and involve invasive procedures. Recently, a novel mesenchymal stem cell derived from human menstrual blood (MenSC) has been discovered and obtained easily and repeatedly. In this study, we examined whether the MenSCs are able to differentiate into functional HLCs in vitro. After three weeks of incubation in hepatogenic differentiation medium containing hepatocyte growth factor (HGF), fibroblast growth factor-4 (FGF-4), and oncostain M (OSM), cuboidal HLCs were observed, and cells also expressed hepatocyte-specific marker genes including albumin (ALB), α-fetoprotein (AFP), cytokeratin 18/19 (CK18/19), and cytochrome P450 1A1/3A4 (CYP1A1/3A4). Differentiated cells further demonstrated in vitro mature hepatocyte functions such as urea synthesis, glycogen storage, and indocyanine green (ICG) uptake. After intrasplenic transplantation into mice with 2/3 partial hepatectomy, the MenSC-derived HLCs were detected in recipient livers and expressed human ALB protein. We also showed that MenSC-derived HLC transplantation could restore the serum ALB level and significantly suppressed transaminase activity of liver injury animals. In conclusion, MenSCs may serve as an ideal, easily accessible source of material for tissue engineering and cell therapy of liver tissues.  相似文献   

5.
芪蚣抗纤方对免疫性肝纤维化大鼠肝组织病理形态的影响   总被引：4，自引：0，他引：4  
目的:通过用芪蚣抗纤方(QF)对免疫损伤性肝纤维化大鼠治疗前后肝组织病理结构变化的观察,进一步阐明QF抗免疫性肝纤维化机理.方法:采用猪血清腹腔注射法持续8周诱导大鼠免疫性肝纤维化模型,然后应用QF灌胃治疗四周,第十二周起,分批处死动物,取肝组织,常规制备石蜡切片和超薄切片,并对石蜡切片进行HE染色、胶原纤维特殊染色(Mallory)和免疫组织化学染色.光镜及透射电镜观察.结果: QF高低剂量治疗组较模型组肝细胞损伤都有不同程度好转,胶原纤维明显减少.结论:QF可能有保护和修复受损的肝细胞,抑制胶原纤维的形成,具有抗免疫损伤性肝纤维化作用.  相似文献   

6.
To examine the effects of co-culture with bone marrow mesenchymal stem cells on expansion of hematopoietic stem/progenitor cells and the capacities of rapid neutrophil engraftment and hematopoietic reconstitution of the expanded cells, we expanded mononuclear cells (MNCs) and CD34+/c-kit+ cells from mouse bone marrow and transplanted the expanded cells into the irradiated mice. MNCs were isolated from mouse bone marrow and CD34+/c-kit+ cells were selected from MNCs by using MoFlo Cell Sorter. MNCs and CD34+/c-kit+ cells were co-cultured with mouse bone marrow-derived mesenchymal stem cells (MSCs) under a two-step expansion. The expanded cells were then transplanted into sublethally irradiated BDF1 mice. Results showed that the co-culture with MSCs resulted in expansions of median total nucleated cells, CD34+ cells, GM-CFC and HPP-CFC respectively by 10.8-, 4.8-, 65.9- and 38.8-fold for the mononuclear cell culture, and respectively by 76.1-, 2.9-, 71.7- and 51.8-fold for the CD34+/c-kit+ cell culture. The expanded cells could rapidly engraft in the sublethally irradiated mice and reconstitute their hematopoiesis. Co-cultures with MSCs in conjunction with two-step expansion increased expansions of total nucleated cells, GM-CFC and HPP-CFC, which led us to conclude MSCs may create favorable environment for expansions of hematopoietic stem/progenitor cells. The availability of increased numbers of expanded cells by the co-culture with MSCs may result in more rapid engraftment of neutrophils following infusion to transplant recipients. Project supported by NIH-Blood, Heart & Lung (National Institute of Health, USA, IR 01 4L70593-01) and Zhejiang Provincial Science Foundation (No. 011103397), China  相似文献   

7.
INTRODUCTION Congestive heart failure is the end stage of manycardiovascular diseases. Myocardial infarction (MI)is a life-threatening event that may cause suddencardiac death and heart failure. Despite considerableadvances in diagnosis and treatment of heart disease,cardiac dysfunction after MI is still the majorworldwide cardiovascular disorder. Damaged myo-cardium after acute MI is gradually replaced by fi-brotic noncontractile cells to form scar tissue. Thedeveloping ventricul…  相似文献   

8.
Mesenchymal stem/stromal cell(MSC)-based therapy has been regarded as one of the most revolutionary breakthroughs in the history of modern medicine owing to its myriad of immunoregulatory and regenerative properties.With the rapid progress in the fields of osteo-and musculoskeletal therapies,the demand for MSC-based treatment modalities is becoming increasingly prominent.In this endeavor,researchers around the world have devised new and innovative techniques to support the proliferation of MSCs while minimizing the loss of hallmark features of stem cells.One such example is electromagnetic field(EMF)exposure,which is an alternative approach with promising potential.In this review,we present a critical discourse on the efficiency,practicability,and limitations of some of the relevant methods,with insurmountable evidence backing the implementation of EMF as a feasible strategy for the clinically relevant expansion of MSCs.  相似文献   

9.
Objective: Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques. The aim of this study is to investigate the effect of connective tissue growth factor (CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells (MSCs). Methods: A CTGF-expressing plasmid (pCTGF) was constructed and transfected into MSCs. Then expressions of bone morphogenesis-related genes, proliferation rate, alkaline phosphatase activity, and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs. Results: Overexpression of CTGF was confirmed in pCTGF-MSCs. pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs (P<0.05). CTGF induced a 7.5-fold increase in cell migration over control (P<0.05). pCTGF transfection enhanced the expression of bone matrix proteins, such as bone sialo-protein, osteocalcin, and collagen type I in MSCs. The levels of alkaline phosphatase (ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0- and 3.0-fold higher than those of MSCs cultured in OS-medium, significantly higher than those of mock-MSCs and normal control MSCs (P<0.05). Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules. Conclusion: Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs, and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.  相似文献   

10.
建立液态甲醛诱导小鼠肝损伤及其纤维化模型,并初步观察小鼠肝组织的病变过程．将正常昆明小鼠随机分为实验组和对照组．实验组小鼠注射15％的甲醛溶液,注射量为1mL／kg,每周注射两次,并且每天用1％的甲醛溶液喂养．对照组小鼠以纯净水正常喂养,分别在实验开始后的第3、6、8周处死实验组小鼠各4只,肉眼及病理切片观察其肝脏形态的改变,发现小鼠的体重均呈增长趋势．与实验组小鼠比较,对照组小鼠体重增长显著（P〈0．05）．第8周小鼠肝脏出现明显的病变,表面粗糙,颜色暗黄,出现深色斑点．在石蜡切片中可观察到肝脏组织变得松散,窦周隙（Disse’s space）增大．肝星状细胞（hepatic stellate cell,HSC）较对照组明显增多．随着甲醛处理时间的延长,HSC不同程度地增多,肝损伤病变程度越来越严重．  相似文献   

11.
Objective: To investigate the directed transplantation of allograftic bone marrow-derived mesenchymal stem cells (MSCs) in myocardial infarcted (MI) model rabbits. Materials and Methods: Rabbits were divided into 3 groups, heart infarcted model with MSCs transplanted treatment (MSCs group, n=12), heart infarcted model with PBS injection (control group, n=20), sham operation with PBS injection (sham group, n=l 7). MSCs labelled by BrdUrd were injected into the MI area of the MSCs group. The same volume of PBS was injected into the MI area of the control group and sham group. The mortality, LVIDd, LVIDs and LVEF Of the two groups were compared 4 weeks later. Tropomyosin inhibitory component (Tn I) and BrdUrd immunohistochemistry identified the engrafted cells 4 weeks after transplantation. Result: The mortality of the MSCs group was 16.7% (2/12), and remarkably lower than the control group's mortality [35% (7/20) (P＜0.05)].Among the animals that survived for 4 weeks, the LVIDd and LVIDs of the MSCs group after operation were 1.17±0.21 cm and 0.74±0.13 cm, and remarkably lower than those of the model group, which were 1.64±0.14 cm and 1.19±0.12 cm (P＜0.05); the LVEF of the MSCs group after operation was 63±6%, and remarkably higher than that of the model group,which was 53±6% (P＜0.05). Among the 10 cases of animals that survived for 4 weeks in the MSCs group, in 8 cases (80%),the transplanted cells survived in the non MI, MI region and its periphery, and even farther away; part of them differentiated into cardiomyocytes; in 7 cases (70%), the transplanted cells participated in the formation of blood vessel tissue in the MI region. Conclusion: Transplanted allograftic MSCs can survive and differentiate into cardiomyocytes, form the blood vessels in the MI region. MSCs transplantation could improve the heart function after MI.  相似文献   

12.

Objective  

Human embryonic stem cells (hESCs) have recently been reported as an unlimited source of mesenchymal stem cells (MSCs). The present study not only provides an identical and clinically compliant MSC source derived from hESCs (hESC-MSCs), but also describes the immunomodulative effects of hESC-MSCs in vitro and in vivo for a carbon tetrachloride (CCl4)-induced liver inflammation model.  相似文献   

13.

Objective

Mesenchymal stem cell (MSC) transplantation is a promising therapy for ischemic heart diseases. However, poor cell survival after transplantation greatly limits the therapeutic efficacy of MSCs. The purpose of this study was to investigate the protective effect of angiopoietin-1 (Ang1) preconditioning on MSC survival and subsequent heart function improvement after transplantation.

Methods

MSCs were cultured with or without 50 ng/ml Ang1 in complete medium for 24 h prior to experiments on cell survival and transplantation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Hoechst staining were applied to evaluate MSC survival after serum deprivation in vitro, while cell survival in vivo was detected by terminal deoxynucleotidyl transferase biotin-dUPT nick end labeling (TUNEL) assay 24 and 72 h after transplantation. Heart function and infarct size were measured four weeks later by small animal echocardiography and Masson??s trichrome staining, respectively.

Results

Ang1 preconditioning induced Akt phosphorylation and increased expression of Bcl-2 and the ratio of Bcl-2/Bax. In comparison with non-preconditioned MSCs, Ang1-preconditioned cell survival was significantly increased while the apoptotic rate decreased in vitro. However, the PI3K/Akt pathway inhibitor, LY294002, abrogated the protective effect of Ang1 preconditioning. After transplantation, the Ang1-preconditioned-MSC group showed a lower death rate, smaller infarct size, and better heart functional recovery compared to the non-preconditioned-MSC group.

Conclusions

Ang1 preconditioning enhances MSC survival, contributing to further improvement of heart function.  相似文献   

14.
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15.
Therapeutically delivered mesenchymal stem cells (MSCs) improve ventricular remodeling. However,the mechanism underlying MSC cardiac remodeling has not been clearly determined. Congestive heart failure (CHF) was induced in rats by cauterization of the left ventricular free wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 d after injury. Ten weeks later,when compared with sham operation,CHF significantly increased nucleus mitotic index,capilla...  相似文献   

16.
Stem cells constitute an important class of cells in the body that have the ability to perpetuate themselves and remain in an uncommitted state by a process of self-renewal as well as to specialize into new cell types. Their ability to differentiate into multiple cell types marks the tremendous potential of stem cells for tissue repair and organ regeneration. Realization of this potential is rapidly opening up unexplored avenues for curing several ailments including diabetes and neurodegenerative diseases. However, very little is understood about the basic biology of stem cells. For example, what are the biochemical tags that allow us to identify stem cell? Which are the signaling pathways that regulate their function? How does the environment (niche) influence major decisions made by stem cell? Is stem cell therapy the end to all woes, or is there a flip side to the story? This article aims to give an overview of the current status of stem cell research and raises some alarming issues related to stem cell-based therapies.  相似文献   

17.
Background:Bone marrow mesenehymal stem cell(MSC)transplantation is a promising strategy in the treatment of myocardial infarction(MI).However,the time for transplanting cells remains controversial.The aim of this study was to find an optimal time point for cell transplantation.Methods:MSCs were isolated and cultured from Sprague-Dawley(SD) rats.MI model was set up in SD rats by permanent ligation of left anterior descending coronary artery.MSCs were directly injected into the infarct berder zone at 1 h,1 week and 2 weeks after MI,respectively.Sham-operated and MI centrel groups received equal volume of phosphate buffered saline(PBS).At 4 weeks after MI,cardiac function Was assessed by echocardiography;vessel density Was analyzed on hematoxylin-eosin stained slides by light microscopy;the apoptosis of cardiomyocytes Was evaluated by terminal deoxynucleotidy1 transferase-mediated dUTP nick end-labeling(TUNEL) assay;the expressions of proteins were analyzed by Western blot.Results:MSC transplantation improved cardiac function.reduced the apoptosis of cardiomyocytes and increased vessel density.These benefits were more obvious in l-week group than in 1-h and 2-week groups.There are more obvious increases in the ratio of bc1-2/bax and the expression of vascular endothelial growth factor(VEGF)and more obvious decreases in the expression of cleaved-caspase-3 in 1-week group than those in other two groups.Conclusion:MSC transplantation was beneficial for the recovery of cardiac function.MSC transplantation at l week post-MI exerted the best effects on increases of cardiac function,anti-apoptosis and angiogenesis.  相似文献   

18.
目的探讨丹参注射液抗肝纤维化作用机理.方法取40只成年wistar大鼠,利用猪血清腹腔注射法,连续6周,复制免疫性肝纤维化模型.治疗组采用大、小剂量丹参液肌肉注射,其剂量分别为0.3ml/kg和0.15ml/kg,每日一次,连续4周.取肝脏切片,HE和Mollory染色,光镜下观察.检测血清SOD活性、MDA含量和肝功能.结果大剂量治疗组肝细胞空泡减少,胶原纤维大部分消失,SOD活性增高,MDA含量降低,与模型组比较有显著性差异(P＜0.05).结论大剂量肌注丹参液,具有治疗肝纤维化的功能.  相似文献   

19.
Embryonic stem(ES)cells are widely used for different purposes,including gene targeting,cell therapy,tissue repair,organ regeneration,and so on.However,studies and applications of ES cells are hindered by ethical issues regarding cell sources.To circumvent ethical disputes,great efforts have been taken to generate ES cell-like cells,which are not derived from the inner cell mass of blastocyst-stage embryos.In 2006,Yamanaka et al.first reprogrammed mouse embryonic fibroblasts into ES cell-like cells called induced pluripotent stem(iPS)cells.About one year later,Yamanaka et al.and Thomson et al.independently reprogrammed human somatic cells into iPS cells.Since the first generation of iPS cells,they have now been derived from quite a few different kinds of cell types.In particular,the use of peripheral blood facilitates research on iPS cells because of safety,easy availability,and plenty of cell sources.Now iPS cells have been used for cell therapy,disease modeling,and drug discovery.In this review,we describe the generations,applications,potential issues,and future perspectives of iPS cells.  相似文献   

20.
The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 (131I), phosphorous-32 (32P), strontium-90 (90Sr), and yttrium-90 (90Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.  相似文献   

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