骨髓间充质干细胞对肝脏的影响

<正>骨髓间充质干细胞(bone mesenchymal stem cells,BMSCs)是成体干细胞主要类型之一,能产生所有的间质谱系细胞,可修复受损的组织,具有干细胞的特性。近年来,随着BMSCs在治疗慢性肝病中的临床研究以及基础研究的不断深入,对肝-骨轴双向调节模式、骨髓细胞及BMSCs对肝脏的影响也有了进一步的了解。     

间充质干细胞向肝细胞诱导分化的研究进展

间充质干细胞（mesenchymal stem cells,MSCs）作为一种多能干细胞,具有横向分化能力,在组织工程、基因工程以及临床应用上有着巨大的应用价值。我国是肝病大国,肝硬化、肝癌和肝衰竭已成为众多肝病患者的最终归宿。干细胞移植为治疗终末期肝病提供了新的希望,而间充质干细胞以其独特的优势,得到许多研究者的青睐。     

脐血间充质干细胞移植治疗肝硬化的研究进展

肝硬化是严重威胁人类健康的疾病之一,目前尚无一种能够普遍开展的有效阻断该疾病进程的根治措施.干细胞领域的研究进展为肝硬化的治疗带来了契机.具有来源广泛、免疫原性弱、增殖分化能力强等优势的人脐血间充质干细胞(mesenchymal stem cells,MSCs)已在相关的基础及临床研究报道中展现出诱人临床应用价值.本文就脐血MSCs的生物学特性及其在治疗肝硬化方面的应用研究作一综述.     

大鼠骨髓间充质干细胞在急性肝损伤环境中的分化

骨髓中除造血干细胞（HSCs）外，还存在着另外一类干细胞，即间充质干细胞（MSCs）。目前研究表明，MSCs具有横向分化能力，尤其能诱导分化为肝细胞，成了肝干细胞研究的热点，也为临床治疗终末期肝病提供了新思路。目前报道肝脏疾病影响17．5％的人群，终末期肝病的治疗在临床尚没有可行的办法。因此，迫切需要建立一种更有效的治疗方法。本研究探讨了骨髓MSCs在急性肝损伤环境中的分化。     

间充质干细胞治疗肝脏疾病的研究进展

间充质干细胞(MSCs)可应用于治疗急性肝衰竭、终末期肝病和遗传代谢性肝病,旁分泌机制是其治疗肝病的重要机制。MSCs还可以通过调节免疫功能减轻炎症反应、抗肝细胞凋亡、抗肝纤维化、促进内源性肝干细胞分化和刺激内源性肝细胞增殖、促进血管增生等修复肝组织。进一步阐明MSCs的治疗机制,合理设计随机双盲对照临床试验,明确干细胞移植可能的副作用,是其广泛应用于临床的前提。     

骨髓干细胞治疗慢性肝衰竭的研究进展

肝移植是治疗慢性肝衰竭(chronic liver failure,CLF)的有效手段,但因各种原因,其临床应用逐渐受到限制,探索新的治疗手段迫在眉睫.1996年Alison等诱导人骨髓干细胞(bone marrow stem cells,BMSCs)分化肝细胞获得成功,推动了BMSCs治疗CLF研究的快速发展.     

间充质干细胞对心肌损伤修复的研究进展

在过去的10年中,干细胞已成功地应用于治疗各种疾病:胰岛移植治疗糖尿病;利用胚胎神经前体细胞和神经干细胞治疗神经系统疾病(帕金森综合征、癫痫、休克、脊髓损伤);肝细胞和肝的干细胞治疗肝脏疾病.近几年,干细胞移植治疗缺血性心脏病已成为一个热点话题.大量的动物实验和前期临床试验表明这种治疗对心肌细胞再生和心脏血流动力学改变有着明显的疗效.在各种干细胞中,由于骨髓间充质干细胞(mesenchymal stem cells, MSCs)具有取材方便、体外易培养和可诱导分化的特点,对其研究更加广泛和深入.现对MSCs在治疗心肌病中的应用作一综述.     

间充质干细胞在炎性关节炎中的应用前景

间充质干细胞(mesenchymal stem cells,MSCs)是存在于健康人体骨髓、脂肪、脐带、脐血、胎盘等组织中具有多向分化潜能的非造血干细胞,在适宜条件下可诱导分化为软骨细胞、成骨细胞、脂肪细胞、心肌细胞、神经细胞等.近年研究发现MSCs不仅具有多向分化潜力,同时具有强大的免疫调节和抗炎特性,这一特性给多种自身免疫性疾病的治疗带来了希望.本文就MSCs在炎性关节炎中的应用前景做一综述.     

间充质干细胞在系统性硬化的应用前景

间充质干细胞(mesenchymal stem cells,MSCs)多存在于骨髓中,是一类具有多向分化能力及免疫调节作用的细胞.近年来,MSCs在自身免疫性疾病中的应用受到很大关注.研究表明,MSCs分化为血管内皮细胞的能力受损在系统性硬化(systemic sclerosis,SSc)的病理改变中起重要作用.同时,...     

间质干细胞和自身免疫病

造血干细胞在自身免疫病中的研究是近年来的热点之一。骨髓中除了有造血干细胞之外，还存在间质干细胞(ruesenchymal stem cells，MSCs)，它能够分化成多种中胚层来源的间质细胞。对MSCs的生物学特性己进行了广泛深入的研究，通过组织工程技术体外分离和定向培养所需的靶细胞，用于多种疾病的治疗。但MSCs在自身免疫病如系统性红斑狼疮(systemic lupus erythematosus，SLE)、类风湿关节炎(rheumatoid arthritis．RA)中的研究报道较少。本研究对MSCs的生物学和免疫学特性及在自身免疫病中的研究进行综述。     

间充质干细胞分化为肝样细胞的研究进展

肝炎后肝硬化等慢性进展性肝病、急性肝功能衰竭、肝脏代谢性疾病及肝脏恶性肿瘤等终末期肝病的发病率日益上升,美国贝塞斯达回忆宣布肝移植是目前治疗终末期肝病最有效的方法,但由于肝源有限、移植后的免疫排斥反应以及高额费用等限制了这种治疗方法的开展。近年来,随着对干细胞研究的深入,发现间充质干细胞(MSCs)具有向肝样细胞分化的潜能,且安全性、可行性及疗效均显示了较好的应用前景,为终末期肝病的治疗提供了新的途径。本文就MSCs不同组织来源分化特点、体内外分化为肝样细胞研究、分化后的肝样细胞的生物学特性及MSCs分化为肝样细胞的机制、MSCs应用的一些问题作一概述。     

MSCs分化为功能性肝细胞的研究进展

间充质干细胞(mesenchymal stemcells,MSCs)来源于中胚层间充质,广泛存在于骨髓、脐带组织、脐血、外周血、脂肪等组织中.在特定条件下,可以分化为骨、脂肪、神经细胞及肝细胞等多种细胞,进而作为一种替代器官移植的新的治疗方法.近年来,肝硬化等终末期肝病的发病率日益上升,成为影响人类健康的重大疾病之一.肝源紧张、免疫排斥限制了肝移植的临床应用,然而众多研究证实MSCs对肝纤维化、肝硬化等肝病的治疗作用可能与其分化为功能性肝细胞有关,但具体机制尚不十分清楚.本文就MSCs的分化能力及其分化的调控、分子机制和不同来源干细胞对肝纤维化的治疗作用作一综述.     

骨髓间充质干细胞逆转肝纤维化的研究进展

骨髓间充质干细胞是一种来源于骨髓基质的具有多向分化能力的干细胞,在特定条件下,可以分化为骨细胞、软骨细胞、脂肪细胞、神经元样细胞及肝细胞等.近年研究表明,骨髓间充质干细胞能抑制和减轻肝纤维化,并且具有免疫抑制和诱导免疫耐受的作用.因此,在细胞移植治疗终末期肝病方面具有广阔的临床应用前景.     

Stem cell transplantation for the treatment of end-stage liver disease

The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer,liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease. Several clinical trials have indicated the efficacy profiles of stem cell transplantation in patients with end-stage liver disease, including liver cirrhosis, liver failure, and liver tumors. Animal models of acute liver failure have also provided important insights into the safety,mechanisms, and efficacy of stem cell therapies. Nevertheless, excitement due to this promising field must be tempered with careful and calculated research. In particular, studies on the quality, safety, and efficacy of stem cell transplantation are needed to ensure that qualified products are tested in well-designed clinical trials and approved by governments. Therefore, further investigations are required to effectively balance the safety with the innovation of stem cell transplantation research toward the effective treatment of end-stage liver disease.     

Role of BMSCs in liver regeneration and metastasis after hepatectomy

Hepatocellular carcinoma(HCC),which develops from liver cirrhosis,is highly prevalent worldwide and is a malignancy that leads to liver failure and systemic metastasis.While surgery is the preferred treatment for HCC,intervention and liver transplantation are also treatment options for end-stage liver disease.However,the success of partial hepatectomy and intervention is hindered by the decompensation of liver function.Conversely,liver transplantation is difficult to carry out due to its high cost and the lack of donor organs.Fortunately,research into bone-marrow stromal cells(BMSCs)has opened a new door in this field.BMSCs are a type of stem cell with powerful proliferative and differential potential that represent an attractive tool for the establishment of successful stem cell-based therapy for liver diseases.A number of different stromal cells contribute to the therapeutic effects exerted by BMSCs because BMSCs can differentiate into functional hepatic cells and can produce a series of growth factors and cytokines capable of suppressing inflammatory responses,reducing hepatocyte apoptosis,reversing liver fibrosis and enhancing hepatocyte functionality.Additionally,it has been shown that BMSCs can increase the apoptosis rate of cancer cells and inhibit tumor metastasis in some microenvironments.This review focuses on BMSCs and their possible applications in liver regeneration and metastasis after hepatectomy.     

Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis

We have demonstrated that adipose tissue-derived mesenchymal stem cells (ADSCs) from mice are capable of reconstituting the hematopoietic microenvironment, and facilitate hematopoiesis more effectively than bone marrow-derived mesenchymal stem cells (BMSCs) in mouse. The ready accessibility of fat tissue rich in MSCs and the higher hematopoiesis-supporting capacities of ADSCs suggest that ADSCs might represent a new therapeutic modality for the regeneration of impaired hematopoiesis. As a further step towards their use in clinical practice, we established human BMSCs and ADSCs from healthy volunteers of similar age, and compared their proliferation capacities, hematopoiesis-supporting properties, and safety. In vitro cell proliferation studies revealed that ADSCs have a higher population doubling number than BMSCs. In vitro co-culture assays showed that ADSCs not only support human CD34(+) peripheral blood stem cells (PBSCs), but also yield significantly more non-adherent hematic cells than BMSCs. In vitro progenitor assays revealed that ADSCs promote a higher frequency of early progenitors than do BMSCs. Interestingly, BM cellularity in irradiated mice that had received ADSCs tended to be higher than that of mice treated with BMSCs. When MSCs were injected into the BM cavity of tibiae, we observed no evidence of MSC-induced toxicity either during or after treatment. In addition, no microscopic abnormalities were observed in the bone marrow and major organs.     

Mesenchymal stem cell therapy for cirrhosis: Present and future perspectives

Cirrhosis occurs as a result of various chronic liver injuries, which may be caused by viral infections, alcohol abuse and the administration of drugs and chemicals. Recently, bone marrow cells (BMCs), hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) have been used for developing treatments for cirrhosis. Clinical trials have investigated the therapeutic potential of BMCs, HSCs and MSCs for the treatment of cirrhosis based on their potential to differentiate into hepatocytes. Although the therapeutic mechanisms of BMC, HSC and MSC treatments are still not fully characterized, the evidence thus far has indicated that the potential therapeutic mechanisms of MSCs are clearer than those of BMCs or HSCs with respect to liver regenerative medicine. MSCs suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, reverse liver fibrosis and enhance liver functionality. This paper summarizes the clinical studies that have used BMCs, HSCs and MSCs in patients with liver failure or cirrhosis. We also present the potential therapeutic mechanisms of BMCs, HSCs and MSCs for the improvement of liver function.     

细胞移植疗法在肝病中的研究与应用

人们对使用细胞移植疗法恢复肝脏功能的前景寄予厚望,期待其最终能够代替肝脏移植手术.众多学者对成人成熟肝细胞,不同来源干细胞的再生能力方面进行了大量研究,特别是间充质干细胞来源的肝细胞移植疗法在恢复肝脏再生方面的效果在动物模型实验中取得令人鼓舞的结果.本文将对近年来细胞移植治疗各种肝病的机制研究、动物实验以及临床试验等方...     

Emerging roles for multipotent, bone marrow-derived stromal cells in host defense

Multipotent, bone marrow-derived stromal cells (BMSCs, also known as mesenchymal stem cells [MSCs]), are culture-expanded, nonhematopoietic cells with immunomodulatory effects currently being investigated as novel cellular therapy to prevent and to treat clinical disease associated with aberrant immune response. Emerging preclinical studies suggest that BMSCs may protect against infectious challenge either by direct effects on the pathogen or through indirect effects on the host. BMSCs may reduce pathogen burden by inhibiting growth through soluble factors or by enhancing immune cell antimicrobial function. In the host, BMSCs may attenuate pro-inflammatory cytokine and chemokine induction, reduce pro-inflammatory cell migration into sites of injury and infection, and induce immunoregulatory soluble and cellular factors to preserve organ function. These preclinical studies provide provocative hints into the direction MSC therapeutics may take in the future. Notably, BMSCs appear to function as a critical fulcrum, providing balance by promoting pathogen clearance during the initial inflammatory response while suppressing inflammation to preserve host integrity and facilitate tissue repair. Such exquisite balance in BMSC function appears intrinsically linked to Toll-like receptor signaling and immune crosstalk.     

Dental pulp cell bank as a possible future source of individual hepatocytes

Mesenchymal stem cells(MSCs) as a source for regenerative medicine are now the subject of much clinical attention. There are high expectations due to their safety, low tumorigenic risk, and low ethical concerns. MSC therapy has been approved for acute graft-versus host diseases since 2015. Tooth-derived MSCs are known to have a great potential in their proliferation and differentiation capacities, even when compared with bone-marrow-derived MSCs. In particular, stem cells from human exfoliated deciduous teeth(SHEDs) are the best candidates for personal cell banking(dental pulp cell bank), because they can be obtained less invasively in the natural process of individual growth. SHEDs are known to differentiate into hepatocytes. There have been several studies showing the effectiveness of SHEDs on the treatment of liver failure in animal models. They may exert their effects either by repopulation of cells in injured liver or by paracrine mechanisms due to their immuneregulatory functions. Moreover, it may be possible to use each individuals' dental pulp cells as a future source of tailor-made differentiated hepatocytes in the context of a bioartificial liver or liver-on-a-chip to screen for drug toxicity.