脐血干细胞移植对严重冠心病患者左心室重塑的改善作用

目的 研究异体脐带血干细胞(UCBSC)移植对严重冠心病患者左心室重塑的作用.方法 将40例冠状动脉造影为三支血管弥漫病变的冠心病患者随机分为对照组和UCBSC组,均给予常规内科药物治疗,UCBSC组在此基础上经冠状动脉前降支移植UCBSCs.移植前、移植后48 h、4周、12周分别检测血清Ⅰ型前胶原羧基端肽(PICP)、Ⅲ型前胶原氨基末端前肽(PCⅢNP)和血管内皮生长因子(VEGF)水平,用心脏超声检测左室舒张末期内径(LVEDd)、左室收缩末期内径(LVESd)和左室射血分数(LVEF)值.结果 UCBSC组患者均未发现过敏反应及移植相关不良反应.与对照组及移植前相比,UCBSC组在移植后48 h血清VEGF水平显著升高(P＜0.01),血浆PICP、PCⅢNP水平降低(P＜0.01),且VEGF变化与PICP、PCⅢNP呈负相关(P＜0.01).移植后12周,UCB-SC组LVESd小于对照组(P＜0.05),但LVEF差异无统计学意义.结论 严重冠心病患者经冠脉移植异体UCB-SCs安全有效,通过上调VEGF表达可抑制心脏纤维化,从而改善左室重塑.     

自体骨髓干细胞移植治疗慢性肝衰竭护理与观察

慢性肝衰竭是在慢性肝病的基础上出现肝细胞大面积坏死进而发生肝功能衰竭的严重肝脏疾病,病死率极高.治疗慢性肝衰竭,肝脏移植是目前最为有效的方法,但由于供体缺乏、费用昂贵,大部分患者难以承受.自体骨髓干细胞移植治疗,具有操作方便、不存在免疫排斥反应等特点,是一种简便、安全、有效的治疗方法,为肝功能衰竭的治疗提供了一个新的研究方向.我院自2005年2月至2006年10月对40例慢性肝衰竭患者采用自体骨髓干细胞移植介入治疗,移植后多数患者临床症状和肝功能均有明显改善,现将护理与观察情况报告如下.     

干细胞移植在消化系统疾病治疗中的应用

干细胞是具有广泛自我更新、自我维持能力的细胞群,根据此特性,临床上应用自体或异体干细胞移植给损伤的受体以达到对受体治疗的目的.将干细胞移植在消化系统疾病治疗中的应用作一综述,讨论了干细胞移植在肝脏疾病、重症急性胰腺炎、炎症性肠病、胃肠动力障碍性疾病、胃食管返流病(GERD)、胃瘫、肠道疾病等的治疗作用.     

干细胞在肝损伤中的机制研究

<正>常的肝细胞和胆管上皮细胞(胆管上皮细胞)处于静态状态。但是肝脏在面对大规模的实质细胞损失时是一个具有高度再生能力的器官。在肝损伤及肝功能受损时,成熟肝细胞分化增殖是恢复动态平衡的第一道防线。尽管肝脏功能较正常肝脏时降低,但肝移植的研究表明,移植的肝细胞有生存优势,在增殖中占主导地位。但是肝移植患者数目的增加,肝源匹配困难等问题的凸显迫使我们不得不采用新的治疗手段刺激肝脏再生,延长终末期肝病患者的生存期。最近研究证实,在终末期肝病患者和肝病模型中,干细胞在肝损伤修复中有重要作用,干细胞移植被看作为一个潜在的替代移植技术。然而,我们对肝脏干细胞、骨髓间充质干细胞的理解目前仍处于起步阶段。一方面,不断有文献证实肝脏干细胞可以成为肝星状细胞和肌成纤维细胞论证。另一方面,干细胞研究的不断深入,应用的更加谨慎也因为它可能显示出肝脏细胞癌的细胞特性。本篇综述将阐述在肝脏损伤后干细胞肝向分化的作用机制,重点阐述相关信号通路,以促进未来靶向治疗研究。     

肝干细胞研究进展

目前对肝硬化、肝功能衰竭等患者除了用肝脏移植手术以外缺乏有效的治疗手段，各种人工肝支持也只能在短期内维持患者的生命，但是肝脏器官移植中供体肝脏的来源十分有限，而研究发现移植入肝硬化等疾病患者的肝细胞具有增殖形成克隆的能力，故人们对用肝细胞的移植来治疗肝病寄予厚望，对肝干细胞的研究为肝病的细胞移植、肝脏组织工程和基因治疗提供了新的思路，带来了新希望。     

造血干细胞移植探析

近年来,干细胞移植和器官移植技术已成为多种疾病的重要治疗手段之一,特别是干细胞(stem cell)工程技术的发展使过去尚不能治愈的许多疾病有了彻底康复的希望。随着细胞分子生物学和细胞克隆新技术的发展与应用,许多组织干细胞已经识别,调节它们生长、分化及其功能的细胞因子相继发现,这使干细胞移植取得了长足的进步。造血干细胞移植是目前国内外细胞水平研究最多,应用较全面     

脐带血移植治疗缺氧缺血性脑损伤和缺血性脑卒中的研究进展

人脐带血(human umbilical cord blood, HUCB)富含丰富的未成熟干细胞,这些干细胞具有修复受损组织的潜能.HUCB干细胞移植在动物模型中可以产生多种作用:神经保护、神经再生、抗炎、血管再生等作用.目前HUCB干细胞移植已被用于治疗血液系统疾病,其还可以用于神经系统疾病,并已在基础研究方面取得较大进展.本文简要讨论HUCB移植的治疗机制及在缺氧缺血性脑损伤和缺血性脑卒中的研究进展.     

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。     

通过蛋白质转运改善肝干细胞移植效果

法国INSERM研究人员设计出一种嵌合蛋白,可通过促进细胞的存活、迁移和增殖来提高干细胞移植效果。该项研究成果刊登在Experimental Biologyand Medicine2009年9月份期刊上,结果显示嵌合蛋白TAT-Tpr-Met可以穿透细胞膜且具有肝细胞生长因子受体功能,用于肝脏干细胞移植可增加进入小鼠肝脏的干细胞数目。     

自体外周血干细胞移植治疗肝硬化围手术期护理体会

干细胞是一类具有自我复制能力的多潜能细胞,在一定条件下,可以分化为220种功能细胞,形成任何类型的组织或器官,即具有极大的"可塑性"和再生能力成为各种组织或器官的潜能.干细胞移植是从患者外周血中分离出干细胞,并将干细胞经肝动脉输入病变肝脏内,在肝脏环境调节下分化为干细胞,从而改善了患者的肝功能.我科于2010年9月-2011年3月共收治肝硬化自体干细胞移植患者40例.现将护理体会介绍如下.     

An update on hepatic stem cells: bench to bedside

Liver failure results in impairment of many functions and dependent organs such as brain and kidneys begin to fail, reducing the chance of recovery even further. Orthotopic liver transplantation (OLTx) is the only treatment that improves the survival rate in patients with liver failure. Liver Transplantation (LT), including orthologous liver transplantation (OLT), cadaveric LT, split LT, living donor LT (LDLT) brings hopes to patients with these diseases. Globally, 1.4 million deaths occur annually as a result of chronic liver diseases. The reasons for this high death toll include unavailability of healthy liver donor and highly expensive liver transplantation treatment. Furthermore, some other factors such as operative risks and post-transplant rejection are major limitation of OLT. Isolated hepatocyte transplantation is emerging as alternative bridge support till the healthy donor is arranged. Mature hepatocytes have several drawbacks such as low proliferation both in vitro and in vivo, low viability after cryopreservation, and requirement of large number of cells for infusion. The studies on isolation of hepatic progenitors have shown promising results to overcome these limitations. These cells possess higher proliferative capacity, are less immunogenic and more resistant to cryopreservation, and ischemic injury; properties that could enhance their engraftment within the recipient liver. The hepatic progenitors have been isolated from the intra-hepatic sources and extra-hepatic sources. Fetal cells are one of the ideal sources of hepatic stem/progenitor cells. Autologous bone marrow stem cell transplantation in patients with cirrhosis has shown promising result.     

Therapeutic potential of endothelial progenitor cells for cardiovascular diseases

In the past decade, researchers have defined committed stem or progenitor cells from various tissues, including bone marrow, peripheral blood, brain, liver and reproductive organs, in both adult animals and humans. Recently, endothelial progenitor cells (EPCs) were isolated from peripheral blood mononuclear cells and were shown to be incorporated into foci of neovascularization. This finding that circulating EPCs may home into sites of neovascularization and differentiate into mature endothelial cells in situ is consistent with the concept of 'vasculogenesis' and suggests that vasculogenesis and angiogenesis might constitute complementary mechanisms for postnatal neovascularization. Furthermore, experimental and clinical studies on ischemic cardiovascular diseases suggest a therapeutic potential for EPC transplantation. In this review, we summarize the biological features of EPCs and discuss their therapeutic potential for the treatment of cardiovascular diseases.     

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.     

Stem cells as a potential treatment of neurological disorders

The ability of stem cells to participate in brain repair has been increasingly demonstrated in recent studies. Most investigations have aimed to replace damaged neurons and glia by direct transplantation or recruitment of newly generated cells in the adult. However, functional improvements were often a result of stem cell-induced self-repair and neuroprotection, rather than cell replacement. Thus, a far more pragmatic approach in the short term might be to use stem cells as chaperones for degenerating nervous tissues. Additionally, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation. Elucidation and exploitation of this new 'stem cell pharmacology' has the potential to revolutionise treatment of neurological diseases.     

人脐带间充质干细胞旁分泌物质的作用及对肝功能衰竭的影响

脐带间充质干细胞(umbilical cord mesenchymalstem cell, UC-MSC)是从人脐带华尔通胶(Wharton jelly)中分离出的细胞,它可以表达间充质干细胞的表面标志,其生物学特性与骨髓间充质干细胞相似,可以诱导分化为多种细胞.最近国内外学者对UC-MSC的移植及诱导分化治疗进行了大量研究,如在心肌梗死、肾脏及血液系统疾病中的研究.但对UC-MSC旁分泌物质的研究却不多见.此文就UC-MSC的分泌、分化及免疫调节作用、旁分泌物质的作用及对肝功能衰竭的影响和应用前景作一综述.     

自体骨髓干细胞移植结合口服中药治疗慢性肝功能衰竭的研究

目的探讨自体骨髓干细胞移植结合口服中药治疗慢性肝功能衰竭的疗效。方法自体骨髓干细胞在体外分离后移植至体内在肝脏中生长分化为具有功能的肝细胞,结合口服中药治疗。结果使损伤的肝功能恢复重构。结论自体骨髓干细胞移植,使损伤的肝功能恢复重构,不存在免疫排斥反应,安全有效,价格低廉,具有良好前景。     

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。     

人参皂苷用于肝脏疾病的研究进展

人参皂苷是五加科人参属人参的主要有效成分,目前发现其单体多达150余种,且不同人参皂苷单体的药理作用也各有差异。人参皂苷主要有抗肿瘤、抗老年痴呆等作用。近年来的研究表明,人参皂苷在肝脏疾病如肝癌、肝纤维化、肝损伤和肝炎等,以及肝移植与肝脏切除中已经显现出一定的治疗作用。人参皂苷在肝脏疾病中的作用机制较为复杂,主要是通过抗氧化、抗炎等作用来保护肝细胞和调节肝功能。本文在查阅国内外文献的基础上,综述了人参皂苷在肝脏疾病治疗中的研究进展,同时就其作用机制进行了阐述,以期为该成分在肝脏疾病中的进一步研究提供参考。     

Bone marrow transplantation: a new strategy for intractable diseases

Bone marrow transplantation is becoming a powerful strategy for the treatment of hematologic disorders (leukemia, aplastic anemia, etc.), congenital immunodeficiencies, metabolic disorders and also autoimmune diseases. Using various animal models for autoimmune diseases, we have previously found that allogeneic (not autologous) bone marrow transplantation can be used to treat autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, immune thrombocytic purpura, insulin-dependent diabetes mellitus, chronic glomerulonephritis and certain types of non-insulin-dependent diabetes mellitus. In contrast, we have found that the transplantation of T-cell-depleted bone marrow cells or partially purified hemopoietic stem cells from autoimmune-prone mice to normal mice leads to the induction of autoimmune diseases in the recipients. These findings have recently been confirmed even in humans; autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and Crohn's disease were resolved after allogeneic bone marrow transplantation. However, there have recently been reports on the rapid recurrence or persistence of autoimmune diseases after autologous bone marrow transplantation. Conversely, the adoptive transfer of autoimmune diseases such as myasthenia gravis, insulin-dependent diabetes mellitus and Graves' disease by allogeneic bone marrow transplantation from donors to recipients has been reported. Owing to these findings, we have proposed that autoimmune diseases are "stem cell disorders." We have thus succeeded in treating autoimmune diseases in various autoimmune-prone mice, except MRL/lpr mice, by conventional bone marrow transplantation. The MRL/lpr mouse itself is radiosensitive (<8.5 Gy), while the abnormal hemopoietic stem cells of the MRL/lpr mouse are radioresistant (>8.5 Gy); conventional bone marrow transplantation (8.5 Gy plus bone marrow transplantation) has a transient effect on autoimmune diseases, which recur three months after the bone marrow transplantation. However, bone marrow transplantation plus bone grafts (to recruit donor stromal cells) completely prevents the recurrence of autoimmune diseases in MRL/lpr mice. Donor-derived stromal cells (including mesenchymal stem cells) thus seem to play a crucial role in successful allogeneic bone marrow transplantation, since there is a major histocompatibility complex restriction between hemopoietic stem cells and stromal cells. We have, however, found that the combination of bone marrow transplantation plus bone grafts has no effect on the treatment of autoimmune diseases in MRL/lpr mice, since MRL/lpr mice become more radiosensitive after the onset of lupus nephritis due to the development of uremic enterocolitis. To reduce the cytotoxic effect of radiation on the intestine, we carried out fractionated irradiation and devised a new strategy. We injected allogeneic whole bone marrow cells (including a small number [<3%] of T cells, hemopoietic stem cells and stromal cells) from donors directly into the intra-bone marrow of recipients so that donor-derived hemopoietic cells including stromal cells could effectively accumulate in the bone marrow. All the MRL/lpr mice survived more than one year (>60 weeks after birth) without the recurrence of autoimmune diseases, and immunological functions were completely restored even when the radiation dose was reduced to 5 Gy x 2. These findings suggest that intra-bone marrow injection-bone marrow transplantation can be used to treat intractable autoimmune diseases under reduced radiation doses without using any immunosuppressants.Intra-bone marrow injection-bone marrow transplantation seems to be the best strategy for allogeneic bone marrow transplantation: 1) no graft-versus-host disease develops even if T cells are not depleted from the bone marrow; 2) no graft failure occurs even if the dose of radiation as the conditioning for bone marrow transplantation is reduced to 5 Gy x 2; 3) hemopoietic recovery is rapid; and 4) T-cell functions are completely restored even in donor-recipient combinations across the major histocompatibility complex barriers. Using cynomolgus monkeys, we have recently established a new method (the "perfusion method") for collecting bone marrow cells from the long bones (femur, humerus, etc.) without peripheral blood contamination. This method has various advantages: 1) no graft-versus-host disease develops even in cynomolgus monkeys, since the percentage of T cells in the bone marrow cells collected is less than 3%; 2) a large number of bone marrow cells can be collected quickly and safely; and 3) the bone marrow cells collected contain stromal cells including mesenchymal stem cells. We therefore believe that this method (intra-bone marrow injection-bone marrow transplantation in conjunction with the perfusion method) will become a powerful new strategy for not only allogeneic bone marrow transplantation but also organ transplantation in conjunction with bone marrow transplantation. Furthermore, this method could become a valuable strategy in regeneration therapy for injured organs and tissues (myocardial infarction, cerebral infarction, Alzheimer's disease, etc.), since it can efficiently reconstitute the recipient with both donor-derived hemopoietic stem cells and mesenchymal stem cells.     

自体外周血干细胞对肝硬化患者肝纤维化的改善作用

目的 探讨自体外周血干细胞对肝硬化患者肝纤维化的治疗作用.方法 选择肝硬化失代偿期患者35 例,在内科综合治疗的基础上予自体外周血干细胞治疗作为A组,常规治疗20例作为B组(对照组).A组经肝动脉将细胞悬液移植入肝脏,分别在治疗前与治疗后第8周、第24周检测肝硬化患者的肝纤维化指标.结果 A组在治疗后第8周,肝纤维化指...