干细胞移植治疗急性心肌梗死是短期有效还是长期有效——国内临床研究现状

干细胞移植在治疗急性心肌梗死方面已经表现出传统治疗方法无可比拟的优越性。文章总结了国内临床研究中干细胞移植疗效的判断,针对干细胞移植技术、干细胞移植类型、移植治疗急性心肌梗死类型等进行分析。国内研究已证实,干细胞移植治疗急性心肌梗死,可以有效地减少心肌梗死缺血面积,减轻左室重构,改善心功能,具有很好的近期疗效和远期疗效。     

Role of mesenchymal stem cells in hematopoietic stem cell transplantation

Within the bone marrow stroma are multipotential cells which are capable of differentiation into a number of mesenchymal cell lineages. These cells, termed mesenchymal stem cells, have recently been identified and characterized in humans. Many studies indicate that the bone marrow stroma is damaged following bone marrow transplantation. Since the marrow stroma is critical for the maintenance of hematopoiesis, its ability to support hematopoiesis following stem cell transplantation may be impaired. Animal models suggest that the transplantation of healthy stromal elements, including mesenchymal stem cells, may enhance the ability of the bone marrow microenvironment to support hematopoiesis after stem cell transplantation. Here the authors review recent data that suggest that mesenchymal stem cells may possess therapeutic value not only for the repair of damaged mesenchymal tissues following hematopoietic stem cell transplantation, but also as potential vectors for the delivery of corrective genes.     

干细胞移植在炎症性肠病治疗中的应用

随着干细胞和炎症性肠病(IBD)研究的深入,干细胞移植在IBD治疗中的应用取得一些进展。此文主要介绍了自体造血干细胞移植,同种异基因造血干细胞移植和间充质干细胞移植在IBD治疗中的应用。     

Role of autologous stem cell transplantation in chronic lymphocytic leukemia

Autologous hematopoietic stem sell transplantation is increasingly considered for treatment of patients with high-risk chronic lymphocytic leukemia. Patients not eligible for allogeneic hematopoietic stem cell transplantation with poor prognosis disease, documented chemosensitivity, and a minimal tumor burden at the time of hematopoietic stem cell transplantation can be treated with autologous hematopoietic stem cell transplantation currently using peripheral blood stem cells. Different purging methods to obtain sources of stem cells free of tumor contamination are currently being evaluated. Major concerns are judicious selection of which patients may benefit from this approach, the subsequent risk of relapse of disease, and the long-term risk of development of secondary malignancies, including myelodysplastic syndrome and acute myelogenous leukemia. Recognizing and reducing the risk factors that contribute to relapse and complications of the procedure should improve outcome after autologous hematopoietic stem cell transplantation. With the increasing use, increasing effectiveness, and low treatment-related mortality associated with nonmyeloablative conditioning regimens, the question of whether a patient should be offered autologous or allogeneic hematopoietic stem sell transplantation can be a difficult one. Defining salvage settings for relapse and implementing a tandem autologous/allogeneic hematopoietic stem cell transplantation approach may provide a method to improve outcome for selected patients.     

Treatment of Lymphoid Malignancies with Non-myeloablative Stem Cell Transplantation

The traditional approach to allogeneic hematopoietic stem cell transplantation involves the administration of myeloablative preparative regimens. This form of conditioning is associated with a relatively high incidence of regimen-related toxicity. As a result, candidates for allogeneic stem cell transplantation may be excluded owing to advanced age or co-morbid medical illness. Recently, so-called "non-myeloablative" regimens have been introduced, where less intense conditioning therapy is used in an attempt to reduce regimen-related toxicity. In addition, non-myeloablative transplantation takes advantage of the graft-versus-tumour effect that is characteristic of allogeneic stem cell transplantation. We review the background, available clinical data, and future directions in non-myeloablative stem cell transplantation, and focus on its potential use in the treatment of lymphoid malignancies.     

Sustained telomere erosion due to increased stem cell turnover during triple autologous hematopoietic stem cell transplantation

Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results regarding the persistence of telomere shortening. Here we have prospectively studied telomere length and proliferation kinetics of hematopoietic cells in aggressive non-Hodgkin lymphoma patients who underwent a four-course high-dose chemotherapy protocol combined with triple autologous stem cell transplantation. We observed sustained telomere shortening in hematopoietic cells after triple stem cell transplantation with prolonged stem cell replication during the first year after stem cell transplantation.     

Treatment of lymphoid malignancies with non-myeloablative stem cell transplantation

The traditional approach to allogeneic hematopoietic stem cell transplantation involves the administration of myeloablative preparative regimens. This form of conditioning is associated with a relatively high incidence of regimen-related toxicity. As a result, candidates for allogeneic stem cell transplantation may be excluded owing to advanced age or co-morbid medical illness. Recently, so-called "non-myeloablative" regimens have been introduced, where less intense conditioning therapy is used in an attempt to reduce regimen-related toxicity. In addition, non-myeloablative transplantation takes advantage of the graft-versus-tumour effect that is characteristic of allogeneic stem cell transplantation. We review the background, available clinical data, and future directions in non-myeloablative stem cell transplantation, and focus on its potential use in the treatment of lymphoid malignancies.     

G-CSF促进Thy1.1+干细胞对球囊损伤后动脉的修复

目的: 探讨粒细胞集落刺激因子（G-CSF）动员自体干细胞及大鼠Thy1.1干细胞局部移植对大鼠颈总动脉球囊损伤后内膜增生的影响,评价干细胞移植对血管再狭窄的作用;探讨G-CSF与Thy1.1干细胞移植是否具有协同作用？G-CSF是否可以促进Thy1.1干细胞对动脉球囊损伤后的修复作用？方法: 将120只雌性大鼠随机分为4组(每组30只),即G-CSF组:于大鼠颈总动脉球囊损伤前7 d,开始皮下注射G-CSF 30 μg/(kg·d),连续注射7 d后进行球囊损伤;干细胞移植组:于颈总动脉球囊损伤后即刻,将约5×106 Thy1.1干细胞(来自4~6周SD大鼠)注入至损伤血管局部;联合移植组:按上述G-CSF组和干细胞移植物的要求,分别注射(入)G-CSF和Thy1.1干细胞;对照组:于颈总动脉球囊损伤后,局部注入等量的生理盐水。各组于术后即刻、3 d、7 d、14 d、28 d,取损伤血管段,HE染色后光镜下检查其病理变化,观察细胞的增殖。用原位杂交方法检查移植细胞的定植、分化情况;并通过RT-PCR方法分析内皮型一氧化氮合酶（eNOS）mRNA的表达。结果: G-CSF组及干细胞移植组内膜增生程度均低于对照组（P<0.05,P<0.01）,eNOS mRNA表达明显高于对照组（P<0.05,P<0.01）。联合移植组内膜增生的程度低于其他组（P<0.05,P<0.01）,eNOS mRNA的表达明显高于其他组（P<0.05,P<0.01）。结论: G-CSF动员自体干细胞及Thy1.1干细胞局部移植可促进大鼠颈总动脉球囊损伤后再内皮化的进程,抑制内膜增生过程,对球囊损伤具有修复作用,可预防血管成形术后的再狭窄。G-CSF与Thy1.1干细胞移植具有协同作用,G-CSF可促进Thy1.1干细胞对动脉球囊损伤后的修复作用。     

Bone marrow transplantation for the treatment of immune deficiency states

The first successful allogeneic bone marrow transplants were performed in children with severe combined immune deficiency (SCID). Bone marrow transplants for patients with SCID have been in the forefront of clinical bone marrow transplantation including the first successful use of T lymphocyte-depleted haploidentical bone marrow and matched unrelated donors. Successful bone marrow transplantation for most forms of SCID requires only the engraftment of donor lymphoid stem cells; donor hematopoietic stem cell engraftment is usually not required. The Wiskott-Aldrich syndrome was the first genetic disease involving the hematopoietic stem cell to be completely corrected by allogeneic bone marrow transplantation. The successful transplantation of Wiskott-Aldrich syndrome patients demonstrated that agents with adequate anti-lymphoid and hematopoietic stem cell activity were necessary in order to achieve complete donor lymphoid and hematopoietic stem cell engraftment. Initially, total body irradiation and now busulfan are used to ablate recipient hematopoietic stem cells, while cyclophosphamide is used to ablate recipient lymphoid stem cells. No single agent/drug is capable of eliminating both stem cell populations. Histocompatible bone marrow transplantation has a role in the treatment of patients with immune deficiency due to primary defects of the hematopoietic stem cell. The recent introduction of cytokines (gamma-interferon and granulocyte colony stimulating factor) may reduce the need for bone marrow transplantation for myeloid immune deficiency states. Initial attempts to treat patients with the acquired immune deficiency syndrome by bone marrow transplantation were limited by the lack of effective concomitant anti-viral therapy. Bone marrow transplantation for immune deficiency states continues to be in the forefront of human bone marrow transplantation.     

Homeostasis of telomere length rather than telomere shortening after allogeneic peripheral blood stem cell transplantation

Hematopoietic reconstitution after stem cell transplantation requires excessive replicative activity because of the limited number of stem cells that are used for transplantation. Telomere shortening has been detected in hematopoietic cells after bone marrow transplantation. This has been thought to result from excessive replication of the stem cells, with putative concomitant reduction of their replicative potential. Hematopoietic stem cells from cytokine-mobilized peripheral blood are increasingly used for stem cell transplantation. These grafts contain higher numbers of hematopoietic stem cells, resulting in a faster hematopoietic reconstitution. We have performed a combined prospective and cross-sectional study of hematologic recovery and telomere length dynamics in the immediate reconstitution period after allogeneic T-cell-depleted blood stem cell transplantation. We analyzed hematologic recovery and telomere length of granulocytes, monocytes, B cells, and T-cell subsets in 30 donor/recipient combinations. We found fast recovery in combination with transient telomere shortening in the myeloid lineages. This initial reduction of telomere length was followed by an increase in telomere length to such an extent that 1 year after transplantation the telomere length in recipient cells was similar to the telomere length in donor-derived cells. Therefore, our data indicate telomere length homeostasis after peripheral blood stem cell transplantation, implying no loss of replicative capacity of the stem cells. Our data indicate that fast expansion is accompanied by a reduction of telomere length and that telomere length homeostasis is achieved by de novo generation of hematopoietic cells from stem cells without transplantation-related telomere loss.     

Stem Cells in the Infarcted Heart

Stem cell transplantation is currently generating a significant interest for use in the future treatment of cardiovascular diseases. Stem cell populations are rapidly increasing, and we are still in the search of optimal cell types to use in clinical trials as bone marrow stem cells did not show significant improvement in cardiac function following transplantation. Experimental stem cell studies raised the question on the true differentiation of tissue-specific cell types following transplantation. In fact, recent studies suggest that improved cardiac function is associated with inhibition of apoptosis and fibrosis provided by factors released from stem cells following transplantation. In this review, we will discuss the effects of transplanted stem cells on engraftment and differentiation as well as factors released from stem cells on apoptosis and cardiac remodeling.     

Alternative haematopoietic stem cell sources for transplantation: place of umbilical cord blood

Umbilical cord blood has rapidly become a valuable alternative stem cell source for allogeneic haematopoietic stem cell transplantation. Extensive research over the last 20 years has established the safety and efficacy of umbilical cord blood transplantation in both children and adults with a variety of malignant and non-malignant diseases. This research has clearly shown that this stem cell source has several unique characteristics resulting in distinct advantages and disadvantages when compared to transplantation with unrelated bone marrow or peripheral blood stem cells. This article reviews the most recent literature comparing the outcomes after umbilical cord blood transplantation with other alternative stem cell sources.     

干细胞移植治疗急性心肌梗死的临床研究新进展

干细胞移植已成为治疗心肌梗死的研究热点。大量临床试验已证实干细胞移植能增加左室射血分数,改善心功能等。但要将干细胞移植应用于临床中,仍有许多问题尚未解决。     

肝干细胞移植治疗肝脏疾病的研究进展

肝干细胞移植治疗急、慢性肝衰竭为治疗肝衰竭开辟了一个新途径。采用肝干细胞移植治疗肝衰竭,移植的肝干细胞可直接参与修复肝组织或帮助肝脏渡过危险期,为后期肝移植赢得时间。近年来,肝干细胞移植研究取得较大的进展,为这一技术从实验室向临床过渡奠定了基础。笔者就肝干细胞移植治疗肝脏疾病的研究进展进行简要综述。     

Infectious complications after allogeneic stem cell transplantation: epidemiology and interventional therapy strategies--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

The risk of infection after allogeneic stem cell transplantation is determined by the underlying disease, the intensity of previous treatments and complications that may have occurred during that time, but above all, the risk of infection is determined by the selected transplantation modality (e.g. HLA-match between the stem cell donor and recipient, T cell depletion of the graft, and others). In comparison with patients treated with high-dose chemotherapy and autologous stem cell transplantation, patients undergoing allogeneic stem cell transplantation are at a much higher risk of infection even after hematopoietic reconstitution, due to the delayed recovery of T and B cell functions. The rate at which immune function recovers after hematopoietic reconstitution greatly influences the incidence and type of post-transplant infectious complications. Infection-associated mortality, for example, is significantly higher following engraftment than during the short neutropenic period that immediately follows transplantation.     

Stem cell transplantation for autoimmune disease: progress and problems

The current status of stem cell transplantation in rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus, and systemic sclerosis are reviewed. From a large European bone marrow transplant registry, a birds' eye view of stem cell transplantation for autoimmune disease can be obtained. Among 43 rheumatoid arthritis patients, 35 juvenile chronic arthritis patients, 34 systemic lupus erythematosus patients, and 58 systemic sclerosis patients who underwent stem cell transplantation, initial responses in most patients were good to excellent. Although initial transplant related mortality was low for rheumatoid arthritis, somewhat higher rates for juvenile chronic arthritis, systemic lupus erythematosus, and systemic sclerosis may be falling with modifications in the stem cell transplantation regimens. In rheumatoid arthritis and systemic lupus erythematosus treatment, the criteria for patient selection are still not clear and the therapeutic regimens for stem cell transplantation (and whether follow-up treatment is necessary) are not fully defined. In juvenile chronic arthritis, responses are encouraging although little fully published data beyond that from the European Bone Marrow Transplant Registry exist. In systemic sclerosis, criteria for patient selection and a limited number of stem cell transplantation regimens have been agreed on and controlled trials are underway.     

Pure red cell aplasia after ABO-incompatible allogeneic stem cell transplantation in severe aplastic anemia with response to steroids: a case report and literature review

Pure red cell aplasia (PRCA) is a rare complication after ABO-incompatible allogeneic stem cell transplantation, but its mechanism is still unknown. Here we report on a patient with severe aplastic anemia who developed PRCA after HLA-identical but major ABO-mismatched peripheral blood stem cell transplantation. Erythroid engraftment was successful with primary steroid treatment. We concluded that an adequate dose of steroids can be the first line of therapy for PRCA after ABO-mismatched allogeneic stem cell transplantation.     

Infectious risks and outcomes after stem cell transplantation: are nonmyeloablative transplants changing the picture?

PURPOSE OF REVIEW: Opportunistic infections contribute to morbidity and mortality after myeloablative allogeneic stem cell transplantation. The development of nonmyeloablative or toxicity-reduced conditioning regimens for allogeneic hematopoietic stem cell transplantation might change this picture significantly. These regimens are in general highly immunosuppressive, but effects on myelopoiesis and mucosal toxicities are usually reduced compared with myeloablative hematopoietic stem cell transplantation conditioning regimens. This review summarizes the infectious risks associated with each type of hematopoietic stem cell transplantation conditioning regimen, and presents the results of early clinical studies. RECENT FINDINGS: Although the data are preliminary, the results of recent studies suggest that nonmyeloablative conditioning regimens may decrease the risks of bacterial infections associated with mucosal damage and persistent neutropenia; however, risks for late viral and fungal infections persist during severe graft versus host disease. Results of several case reports and series emphasize that therapeutic outcomes of infections may be improved in patients who receive nonmyeloablative conditioning regimens. SUMMARY: Infectious risks and outcomes after hematopoietic stem cell transplantation appear to be in evolution given the introduction of alternative, nonmyeloablative conditioning regimens. Although infections remain a prominent cause of transplant-related mortality, the timing and types of infections may differ. Further studies are necessary to define appropriate preventative strategies, and to determine whether patients with ongoing infections might benefit from nonmyeloablative hematopoietic stem cell transplantation.     

Critical review on non-myeloablative stem cell transplantation (NST)

Allogeneic stem cell transplantation is an established treatment modality for a variety of hematologic malignancies. Unfortunately, it carries a high risk of complications and toxicities related to the intensive preparative regimen which is traditionally used for pre-transplant myeloablation and the graft versus host disease, which may be life threatening. Thus allogeneic stem cell transplantation has been used only for younger patients with a good performance status, excluding many other potential candidates due to advanced age or comorbid conditions. Using reduced intensity preparative regimens for allogeneic stem cell transplantation (non-myeloablative stem cell transplantation (NST)) researchers attempted to overcome these barriers in patients' selection and tried to make hematopoietic stem cell (HSC) transplantation a safer procedure. The well-described graft versus malignancy effect would be the most curative element in this treatment. After more than 5 years of cumulative clinical experience, we know that NST is a feasible treatment option for patients with suboptimal performance status and is mostly effective in slow proliferating malignancies, which gives time for a graft versus malignancy effect to take place. Additionally achievement of stable donor cell engraftment with NSTs provides a platform for adoptive immune cell treatments and is promising for extended indications of stem cell transplantation in the future.     

Long-term endoscopic remission of crohn disease after autologous stem cell transplantation for acute myeloid leukaemia

A favourable course of Crohn disease has been observed after allogeneic bone marrow transplantation. and there is now mounting evidence that autologous stem cell may be an effective treatment for severe autoimmune diseases. Here, we present the first long-term endoscopic follow-up of a patient with Crohn disease undergoing autologous stem cell transplantation for haematological disease. A 54-year-old woman developed Crohn disease and was submitted to ileocaecal resection. Four months after surgery, the patient contracted acute myeloid leukaemia. She was initially treated with chemotherapy, and subsequently underwent autologous stem cell transplantation. Following transplantation, the patient has remained in clinical remission regarding both diseases, without anti-inflammatory medication. She has undergone ileo-colonoscopy with normal findings at 1, 2, 3 and 5 years after transplantation. This case suggests that autologous stem cell transplantation can change not only the clinical course, but also the natural history of intestinal inflammation in Crohn disease. This has pathophysiological as well as therapeutic implications.