间充质干细胞免疫调节在肝纤维化中的治疗作用

肝纤维化是各种病因引起的一种肝内慢性损伤修复反应,细胞外基质的产生和降解失衡是肝纤维化发生、发展的病理生理基础。目前,肝纤维化的发病机制及其治疗仍是研究的热点。间充质干细胞是一类具有高度自我更新和多向分化潜能的成体干细胞,具有一定的免疫调节功能,其通过调节肝细胞再生,下调免疫介导的肝损伤,从而发挥对肝病的治疗作用。本文就间充质干细胞在肝纤维化治疗中的免疫调节作用作一综述。     

骨髓间充质干细胞改善肝纤维化机制的研究进展

肝纤维化以肝脏组织瘢痕为特征,是慢性肝脏疾病发展为肝癌的中间病理过程,发生机制涉及多种信号通路,其逆转性是目前的研究热点。骨髓间充质干细胞(bone marrow mesenchymal stem cells, BMSCs)是一种具有多向分化潜能的成体干细胞,在体内和体外均具备分化为肝样细胞,发挥正常肝细胞功能的能力。现代药理实验研究表明,单独使用BMSCs或联合活性因子、中药或中药单体、基因修饰等方式可以促进其增殖、分化、迁移,提高治疗效果,发挥改善肝纤维化的作用。通过归纳总结现有文献,从肝纤维化发病机制、肝纤维化改善机制、BMSCs生物学特性及其改善机制等方面对BMSCs改善肝纤维化疗效机制进行综述,为后期发展BMSCs细胞疗法提供参考。     

自体骨髓干细胞移植治疗肝硬化研究进展

目的干细胞是一类具有自我更新和分化潜能的细胞,骨髓干细胞(BMSCs)直接来源于成人的骨髓,具有极强的可塑性,自体BMSCs在活体肝脏内可分化为有功能的肝细胞和胆管细胞。BMSCs经分离纯化后移植到肝脏,可以在肝脏内逐渐分化为有功能的肝细胞,逐渐改善肝脏功能,为中、晚期肝硬化治疗提供新途径。本文综述了BMSCs与肝脏的关系、BMSCs在肝脏内分化的条件和机制、BMSCs移植治疗肝硬化的临床前及临床研究,以期为从事肝病研究的临床医生提供肝硬化治疗的新方法和参考依据。     

83例干细胞肝内介入治疗的临床护理

干细胞肝内介入治疗是治疗肝硬化的有效手段之一,干细胞肝内介入治疗是采用患者自体骨髓源性干细胞体外分离后纯化经肝动脉途径移植于患者体内,使干细胞在肝脏中分化生长为具有功能的肝细胞,参与肝功能的修复和重构,使肝     

人源性干细胞分化的神经细胞在药物神经毒性评价中的应用

人源性干细胞可自我更新,且具有多向分化潜能.人多能干细胞可分化为神经元、胶质细胞和类脑器官等,为寻求药物早期筛选和神经毒性临床前评价的新模型提供了可能.目前基于人源性干细胞分化的神经细胞的体外模型已用于药物筛选、有效性和安全性评价以及阐明未知的疾病发生机制,为开展临床试验奠定了良好的基础,并且有助于减少药物临床应用中不...     

自体骨髓干细胞移植治疗下肢缺血性疾病的研究现状

骨髓干细胞是成体干细胞的一种,具有自我更新和分化潜能,在特定条件下可分化为不同的组织细胞或器官,自体骨髓干细胞移植通过增强移植部位组织细胞更新或替换缺损组织来治疗多系统疾病,前景乐观。现就目前自体骨髓干细胞移植治疗下肢缺血性疾病的研究状况进行综述。     

全能干细胞的研究现状与前景

干细胞是具有全能或多能分化潜能（胚胎干细胞ES，EG）和广泛存在于成体器官组织中保留不分化和维持身体自我更新能力（组织干细胞）的特种细胞。由于这种细胞的高度可塑性和在组织修复、疾病的细胞治疗以及生殖遗传工程等方面的潜在应用价值，近年来成为生命科学研究领域中最热点的课题之一。     

干细胞的研究现状和应用展望

成体干细胞在治疗多种难治性疾病包括中风、神经系统变性性疾病、糖尿病、心脏病,外伤等已开辟了一个新的方向.干细胞是研究细胞自我更新和分化的重要工具,并将在新药发明和药物毒性筛选中发挥作用,对成体干细胞及其分化的研究必将在今后对医学及生物学领域产生极其深远的影响。     

脂肪源性干细胞的临床转化研究

脂肪源性干细胞又称脂肪间充质干细胞,是一类处于未定向分化状态并具有自我更新、高度增殖和多向分化潜能的细胞群体,具有一般干细胞的特点,是一种理想的组织工程种子细胞.近年来,对脂肪间充质干细胞的应用研究已经取得了初步进展,其特有的生物学特性为多种疾病的治疗开辟了新的思路.本文就脂肪间充质干细胞的生物学特性及其在临床上的转化研究进行阐述.     

SIRT1与成体干细胞衰老

成体干细胞(adult stem cells)具有自我更新功能并可以分化为执行特定功能的体细胞,维持组织和器官结构完整和功能健全。有研究显示衰老可以出现在成体干细胞水平,并与机体老龄化及损伤修复能力下降有关。哺乳动物沉默调节因子2相关酶1(Sirtuins 1,SIRT1)是NAD+依赖性蛋白去乙酰化酶。对体细胞的研究表明,提高SIRT1活性可以抗细胞衰老。近年来,成体干细胞的相关研究表明SIRT1可能具有平衡干细胞的静息与增殖、维持干细胞自我更新功能、缓解年龄相关性成体干细胞功能下降和抑制成体干细胞分化紊乱的作用,但其抗衰老的分子机制还有待进一步研究。     

Adult neural stem cell therapy: expansion in vitro, tracking in vivo and clinical transplantation

Neural stem cells (NSCs) are present not only in the developing nervous systems, but also in the adult human central nervous system (CNS). It is long thought that the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus are the main sources of human adult NSCs, which are considered to be a reservoir of new neural cells. Recently adult NSCs with potential neural capacity have been isolated from white matter and inferior prefrontal subcortex in the human brain. Rapid advances in the stem cell biology have raised appealing possibilities of replacing damaged or lost neural cells by transplantation of in vitro-expanded stem cells and/or their neuronal progeny. However, sources of stem cells, large scale expansion, control of the differentiations, and tracking in vivo represent formidable challenges. In this paper we review the characteristics of the adult human NSCs, their potentiality in terms of proliferation and differentiation capabilities, as well as their large scale expansion for clinical needs. This review focuses on the major advances in brain stem cell-based therapy from the clinical perspective, and summarizes our work in clinical phase I-II trials with autologuous transplantation of adult NSCs for patients with open brain trauma. It also describes multiple approaches to monitor adult human NSCs labeled superparamagnetic nanoparticles after transplantation and explores the intriguing possibility of stem cell transplantation.     

Stem cells as a treatment for chronic liver disease and diabetes

Advances in stem cell biology and the discovery of pluripotent stem cells have made the prospect of cell therapy and tissue regeneration a clinical reality. Cell therapies hold great promise to repair, restore, replace or regenerate affected organs and may perform better than any pharmacological or mechanical device. There is an accumulating body of evidence supporting the contribution of adult stem cells, in particular those of bone marrow origin, to liver and pancreatic islet cell regeneration. In this review, we will focus on the cell therapy for the diseased liver and pancreas by adult haematopoietic stem cells, as well as their possible contribution and application to tissue regeneration. Furthermore, recent progress in the generation, culture and targeted differentiation of human haematopoietic stem cells to hepatic and pancreatic lineages will be discussed. We will also explore the possibility that stem cell technology may lead to the development of clinical modalities for human liver disease and diabetes.     

Stem cell research in hepatocellular carcinoma

The traditional view that adult human liver tumors, mainly hepatocellular carcinoma (HCC), arise from mature cell types has been challenged in recent decades. The results of several studies suggest that HCC can be derived from liver stem cells. There are four levels of cells in the liver stem cell lineage: hepatocytes, hepatic stem cells/oval cells, bone marrow stem cells and hepato-pancreas stem cells. However, whether HCC is resulted from the differentiation block of stem cells and, moreover, which liver stem cell lineage is the source cell of hepatocarcinogenesis remain controversial. In this review, we focus on the current status of liver stem cell research and their roles in carcinogenesis of HCC, in order to explore new approaches for stem cell therapy of HCC.     

Cell-based therapy for liver diseases

Although liver transplantation has become standard therapy in the treatment of patients with liver failure, several problems should be considered in the management of these patients. Other approaches have been proposed, in particular cellular-based procedures. Isolated hepatocytes may be used instead of whole organ transplantation or integrated within the bioartificial devices, in order to replace the missing synthetic and metabolic liver functions. Moreover patient's own hepatocytes may be ex vivo genetically modified to provide the function of a mutant gene. However, new cell sources alternative to adult hepatocytes are actually under investigation, on the basis of recent advances in the field of liver repopulation. Xenogenic primary cells, human hepatoma cells, immortalized hepatocytes and stem cells have been testing in several experiments, even if up to now none of them represent a "gold-standard" for cell-based treatment of liver diseases. In the next future, it is possible that different clinical situations will require different therapeutic approaches, that will be finally defined from the concomitant advances in the development of artificial devices and liver cell biology.     

Pluripotent stem cell derived hepatocyte like cells and their potential in toxicity screening

Despite considerable progress in modelling human liver toxicity, the requirement still exists for efficient, predictive and cost effective in vitro models to reduce attrition during drug development. Thousands of compounds fail in this process, with hepatotoxicity being one of the significant causes of failure. The cost of clinical studies is substantial, therefore it is essential that toxicological screening is performed early on in the drug development process. Human hepatocytes represent the gold standard model for evaluating drug toxicity, but are a limited resource. Current alternative models are based on immortalised cell lines and animal tissue, but these are limited by poor function, exhibit species variability and show instability in culture. Pluripotent stem cells are an attractive alternative as they are capable of self-renewal and differentiation to all three germ layers, and thereby represent a potentially inexhaustible source of somatic cells. The differentiation of human embryonic stem cells and induced pluripotent stem cells to functional hepatocyte like cells has recently been reported. Further development of this technology could lead to the scalable production of hepatocyte like cells for liver toxicity screening and clinical therapies. Additionally, induced pluripotent stem cell derived hepatocyte like cells may permit in vitro modelling of gene polymorphisms and genetic diseases.     

Stem cell ageing and apoptosis

Ageing has been defined as the process of deterioration of many body functions over the lifespan of an individual. In spite of the number of different theories about ageing, there is a general consensus in identifying ageing effects in a reduced capacity to regenerate injured tissues or organs and an increased propensity to infections and cancer. In recent years the stem cell theory of ageing has gained much attention. Adult stem cells residing in mammalian tissues are essential for tissue homeostasis and repair throughout adult life. With advancing age, the highly regulated molecular signalling necessary to ensure proper cellular, tissue, and organ homeostasis loses coordination and leads, as a consequence, to a compromised potential of regeneration and repair of damaged cells and tissues. Although a complete comprehension of the molecular mechanisms involved in stem cell ageing and apoptosis is far to be reached, recent studies are beginning to unravel the processes involved in stem cell ageing, particularly in adult skeletal muscle stem cells, namely satellite cells. Thus, the focus of this review is to analyse the relationship between stem cell ageing and apoptosis with a peculiar attention to human satellite cells as compared to haematopoietic stem cells. Undoubtedly, the knowledge of age-related changes of stem cells will help in understanding the ageing process itself and will provide novel therapeutic challenges for improved tissue regeneration.     

When stem cells meet immunoregulation

The clinical use of stem cells to prevent tissue injury or reconstruct damaged organs is constrained by different ethical and biological issues. Whereas the use of adult stem cells isolated from differentiated tissues is advantageous from the ethical point of view, the immune response of a host to implants of either embryonic or adult stem cells remains a critical problem. Embryonic stem cells can be rejected by an immunocompetent recipient as well as some types of adult stem cells. There is, however, a population of adult stem cells able to differentiate into the three mesenchymal lineages, osteocytes, chondrocytes, adipocytes that have the additional capacity of modulating the immune response by the activation of disparate mechanisms, among which the generation of antigen-specific CD4+CD25+FoxP3+ regulatory T lymphocytes.This short review will focus on the immunological properties of embryonic and adult stem cells are, with particular emphasis on the immunomodulatory function of mesenchymal stem cells and their interactions with regulatory T lymphocytes.     

Stem cell approaches for the treatment of renal failure

The inadequacy of current treatment modalities and insufficiency of donor organs for cadaveric transplantation have driven a search for improved methods of dealing with renal failure. The rising concept of cell-based therapeutics has provided a framework around which new approaches are being generated, and its combination with advances in stem cell research stands to bring both fields to clinical fruition. This budding partnership is presently in its very early stages, but an examination of the cell-based therapies currently under development clearly shows the magnitude of the role that stem cells will ultimately play. The issue over reports of unexpected plasticity in adult stem cell differentiation remains a focus of debate, and evidence for bone marrow-derived stem cell contributions to renal repair has been challenged. The search for adult renal stem cells, which could have a considerable impact on much of the work discussed here, appears to be narrowing. The use of embryonic tissue in research continues to provide valuable insights but will be the subject of intense societal scrutiny and debate before it reaches the stage of clinical application. Embryonic stem (ES) cells, with their ability to generate all, or nearly all, of the cell types in the adult body and a possible source of cells genetically identical to the donor, hold great promise but face ethical and political hurdles for human use. Immunoisolation of heterologous cells by encapsulation creates opportunities for their safe use as a component of implanted or ex vivo devices.     

Molecular targeting regulation of proliferation and differentiation of the bone marrow-derived mesenchymal stem cells or mesenchymal stromal cells

The bone marrow-derived mesenchymal stem cells or mesenchymal stromal cells (MSCs), with pluripotent differentiation capacity, present an ideal source for cell transplantation or tissue engineering therapies, but exact understanding of regulating mechanism underling MSC proliferation and differentiation remains a critical issue in securing their safe and efficient clinical application. This review outlines current knowledge regarding MSC cell surface biomarkers and molecular mechanisms of MSC differentiation and proliferation with emphasis on Wnt/β-catenin signaling, Notch signaling pathway, bone morphogenesis proteins and various growth factors functioning in regulation of differentiation and proliferation of MSCs. Possible relation of oncogene and immunosuppressive activities of MSCs with tumorigenicity or tumor generation is also addressed for safe translational clinical application. Fast increase of MSC knowledge and techniques has led to some successful clinical trials and helped devising new tissue engineering therapies for bone and cartilage diseases that severely afflict human health. Production of adult MSC-derived functional neurons can further extend their therapeutic application in nerve injury and neurodegenerative diseases. It is promising that MSCs shall overcome ethical and immunorejection problems appeared in human embryonic stem cells, and specific molecular targeting manipulation may result in practical MSC therapy for personalized treatment of various diseases in the regeneration medicine.