hematopoietic

造血
  • 文章类型: Journal Article
    这篇综述的目的是总结目前对干细胞疗法治疗效果的理解,包括造血干细胞,用于治疗缺血性心脏损伤。按照PRISMA准则,我们在MEDLINE进行了电子搜索,和EMBASE。我们筛选了592项研究,包括RCT,观察性研究,以及研究造血干细胞治疗对成年心力衰竭患者的影响的队列研究。涉及儿科患者的研究,间充质干细胞治疗,非心力衰竭(HF)研究被排除在我们的评价之外.在592项研究中,7项研究符合我们的纳入标准。总的来说,给予造血干细胞(通过冠状动脉内或心肌梗死)导致积极的心脏结果,例如病理性左心室重塑的改善,急性心肌梗死后的灌注,和NYHA症状分类。此外,合并死亡,因心力衰竭再次住院,在接受骨髓来源的造血干细胞治疗的患者中,梗死程度显著降低.我们的审查表明,造血干细胞管理可以导致HF患者的心脏结果阳性。未来的研究应旨在增加女性代表性和非缺血性HF患者。
    The purpose of this review is to summarize the current understanding of the therapeutic effect of stem cell-based therapies, including hematopoietic stem cells, for the treatment of ischemic heart damage. Following PRISMA guidelines, we conducted electronic searches in MEDLINE, and EMBASE. We screened 592 studies, and included RCTs, observational studies, and cohort studies that examined the effect of hematopoietic stem cell therapy in adult patients with heart failure. Studies that involved pediatric patients, mesenchymal stem cell therapy, and non-heart failure (HF) studies were excluded from our review. Out of the 592 studies, 7 studies met our inclusion criteria. Overall, administration of hematopoietic stem cells (via intracoronary or myocardial infarct) led to positive cardiac outcomes such as improvements in pathological left-ventricular remodeling, perfusion following acute myocardial infarction, and NYHA symptom class. Additionally, combined death, rehospitalization for heart failure, and infarction were significantly lower in patients treated with bone marrow-derived hematopoietic stem cells. Our review demonstrates that hematopoietic stem cell administration can lead to positive cardiac outcomes for HF patients. Future studies should aim to increase female representation and non-ischemic HF patients.
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  • 自然杀伤(NK)细胞的行为和功能是由一系列广泛的激活和抑制受体产生的负或正信号之间的平衡控制的。包括杀伤细胞免疫球蛋白样受体(KIR)蛋白,先天免疫系统的主要成分,通过产生细胞因子的释放和细胞毒性,对病毒感染的转化细胞产生初始反应。可以肯定的是,KIR是遗传多态性的,个体中KIR多样性的程度可能具有造血干细胞移植(HSCT)的潜在结果。在这方面,最近的研究表明,KIR在恶性疾病的干细胞移植中与其配体(HLA)一样重要。然而,与HLA表位错配不同,这是众所周知的NK同种异体反应性的原因,目前尚不清楚KIR基因在HSCT中的作用。由于KIR基因含量的遗传变异,等位基因多态性,和个体之间的细胞表面表达,根据HLA和KIR谱选择合适的供体对于改善干细胞移植的结局至关重要.此外,需要更全面地研究KIR/HLA相互作用对HSCT结局的影响.本文旨在对NK细胞再生技术进行综述,KIR基因多态性,和KIR-配体结合对单倍体相合干细胞移植后血液系统恶性肿瘤结局的影响。从文献中收集的综合数据可以为KIR匹配状态在移植中的重要性提供新的见解。
    Natural killer (NK) cell behavior and function are controlled by a balance between negative or positive signals generated by an extensive array of activating and inhibiting receptors, including killer cell immunoglobulin-like receptor (KIR) proteins, main components of the innate immune system that contribute to initial responses against viral infected-transformed cells through generation of the release of cytokines and cytotoxicity. What is certain is that KIRs are genetically polymorphic and the extent of KIRs diversity within the individuals may have the potential outcomes for hematopoietic stem cell transplantation (HSCT). In this regard, recent studies suggest that KIR is as imperative as its ligand (HLA) in stem cell transplantation for malignant diseases. However, unlike HLA epitope mismatches, which are well-known causes of NK alloreactivity, a complete understanding of KIR genes\' role in HSCT remains unclear. Because of genetic variability in KIR gene content, allelic polymorphism, and cell-surface expression among individuals, an appropriate selection of donors based on HLA and KIR profiles is crucial to improve outcomes of stem cell transplantation. In addition, the impact of the KIR/HLA interaction on HSCT outcomes needs to be investigated more comprehensively. The present work aimed to review the NK cell regeneration, KIR gene polymorphisms, and KIRligand binding on outcomes in hematologic malignancies following haploidentical stem cell transplantation. Comprehensive data gathered from the literature can provide new insight into the significance of KIR matching status in transplantations.
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  • 文章类型: Journal Article
    干细胞移植(SCT)为自身免疫性疾病的治疗铺平了道路。SCT已在1型糖尿病(T1DM)中作为一种基于自身免疫的疾病进行了研究,但以往的研究并未对其治疗T1DM的效果提出全面的看法。
    本系统评价和荟萃分析在PROSPERO注册后,根据Cochrane的临床试验评估指南进行了搜索,以寻找符合资格的临床试验,这些临床试验调查了PubMed的SCT对T1DM的影响(基于ADA®诊断标准),WebofScience,Scopus,etc,以及2000年1月1日至2019年9月31日的临床试验注册。使用MeSH和EM树项设计了搜索策略。主要结果包括胰岛素总日剂量(TDD)(U/kg)水平的变化,次要结局包括HbA1c的变化,c-肽,并调整HbA1c水平。进行QCochrane检验和I2统计量以评估主要临床试验中的异质性及其严重程度。CochraneROB用于确定偏倚风险,和《Cochrane干预措施系统审查手册》用于全文论文。荟萃分析在STATA软件中完成,结果显示在他们的森林地块上。通过元回归检验对混杂因素进行评估。
    共有9452项研究进行了电子筛选,共纳入35篇论文进行数据提取。这项回顾研究的结果表明,173(26.5%)糖尿病患者经历了无胰岛素期(1至80个月),445(68%)显示SCT后胰岛素的TDD减少。造血干细胞(HSC)与间充质干细胞(MSC)移植的联合与TDD的改善显着相关(SMD:-0.586,95%CI:-1.204/-0.509,I2:0%),HbA1c(SMD:-0.736,95%CI:-1.107/-0.365,I2:0%),调整后的HbA1c(SMD:-2.041,95%CI:-2.648/-1.434,I2:38.4%),和c肽(SMD:1.917,95%CI:0.192/3.641,I2:92.5%)在随访的第3个月,而其相关性在移植后3至12个月有增长趋势。考虑到严重的不良事件,HSC移植伴随调理不能被认为是一种安全的治疗方法。
    T1DM的SCT临床试验大多为单臂。虽然荟萃分析显示SCT与T1DM改善相关,需要精心设计的随机临床试验来阐明其疗效.
    根据这项荟萃分析的结果,MSC及其与HSC的组合可被视为T1DM中SCT的“安全小区”。此外,为了评估SCT的疗效,胰岛素TDD的计算(U/kg/天),c肽的AUC,和调整HbA1c是强烈建议。
    Stem cell transplantation (SCT) has paved the way for treatment of autoimmune diseases. SCT has been investigated in type 1 diabetes mellitus (T1DM) as an autoimmune-based disorder, but previous studies have not presented a comprehensive view of its effect on treatment of T1DM.
    After registration of the present systematic review and meta-analysis in the PROSPERO, a search was done according to the Cochrane guidelines for evaluation of clinical trials to find eligible clinical trials that investigated the effect of SCT on T1DM (based on ADA® diagnostic criteria) from PubMed, Web of science, Scopus, etc, as well as registries of clinical trials from January 1, 2000, to September 31, 2019. A search strategy was designed using MeSH and EM-tree terms. Primary outcome included the changes in the insulin total daily dose (TDD) (U/kg) level, and secondary outcomes included the changes in the HbA1c, c-peptide, and adjusted HbA1c levels. The Q Cochrane test and I2 statistic were performed to assess the heterogeneity and its severity in primary clinical trials. The Cochrane ROB was used to determine risk of bias, and Cochrane Handbook for Systematic Reviews of Interventions was used in the full text papers. The meta-analysis was accomplished in the STATA software, and the results were shown on their forest plots. Confounders were evaluated by the meta-regression test.
    A total of 9452 studies were electronically screened, and 35 papers were included for data extraction. The results of this review study showed that 173 (26.5%) diabetic patients experienced insulin-free period (from 1 to 80 months), and 445 (68%) showed reduction in TDD of insulin after the SCT. Combination of hematopoietic stem cell (HSC) with mesenchymal stem cell (MSC) transplantation were significantly associated with improvement of the TDD (SMD: - 0.586, 95% CI: - 1.204/- 0.509, I2: 0%), HbA1c (SMD: - 0.736, 95% CI: - 1.107/- 0.365, I2: 0%), adjusted HbA1c (SMD: - 2.041, 95% CI: - 2.648/- 1.434, I2: 38.4%), and c-peptide (SMD: 1.917, 95% CI: 0.192/3.641, I2: 92.5%) on month 3 of follow-up, while its association had a growing trend from 3 to 12 months after the transplantation. Considering severe adverse events, HSC transplantation accompanied with conditioning could not be suggested as a safe treatment.
    Most of the clinical trials of SCT in T1DM were single arm. Although meta-analysis illustrated the SCT is associated with T1DM improvement, well-designed randomized clinical trials are needed to clarify its efficacy.
    Based on the results of this meta-analysis, the MSC and its combination with HSC could be considered as \"Safe Cell\" for SCT in T1DM. Furthermore, to evaluate the SCT efficacy, calculation of insulin TDD (U/kg/day), AUC of c-peptide, and adjusted HbA1c are highly recommended.
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  • 文章类型: Journal Article
    BACKGROUND: Crohn\'s disease (CD) is an autoimmune disease of the gastrointestinal tract, characterized by relapsing and remitting courses. The disease is debilitating in nature with three prominent phenotypic clinical presentations; fistulizing, stenosing, and inflammatory. Stem cells offer a new hope for CD patients with modifying the immune response and progression of the healing process.
    OBJECTIVE: This mini-review discusses the role of stem cells in treating CD, their effectiveness as a new therapy and their current limitations faced.
    METHODS: The author conducted a literature review on recent randomized controlled trials and cohort studies concerned with the topic in question using the following keywords (Crohn\'s Disease, perianal fistula, Stem cell therapy, mesenchymal stem cells, remission).
    RESULTS: Clinical trials show that the stem cells are more effective in the CD associated complex perianal fistula than the CD enteritis. Till the time being, there are no standardized guidelines regarding; dose of stem cells used, number of doses administered, route of administration, type of stem cells used. Only one group of researchers proposed a standardized procedure for injecting mesenchymal stem cells in complex perianal fistula, according to their own experience in clinical trials. Moreover, mesenchymal stem cells and their related types (placental, adipose tissue, umbilical tissue, etc.) are the most safe and effective in clinical trials. Currently; the commercially available mesenchymal stem cells preparation (Darvadstrocel (Cx601)) is the only one approved by The United States Food and Drug Administration (FDA) for clinical use in refractory CD associated complex perianal fistula.
    CONCLUSIONS: Stem cell therapy (SCT) shows promise in; inducing remission in refractory Crohn\'s colitis, and perianal fistula, but further research is required before SCT could be applied to clinical practice guidelines.
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  • 文章类型: Journal Article
    Despite of the increasing number of investigations on the effects of acute exercise on circulating stem and progenitor cell (SC) numbers, and in particular on respective subgroups, i.e. endothelial (ESC), hematopoietic (HSC), and mesenchymal (MSC) stem and progenitor cells, a consensus regarding mechanisms and extent of these effects is still missing. The aim of this meta-analysis was to systematically evaluate the overall-effects of acute exercise on the different SC-subgroups and investigate possible subject- and intervention-dependent factors affecting the extent of SC-mobilization in healthy humans. Trials assessing SC numbers before and at least one timepoint after acute exercise, were identified in a systematic computerized search. Compared to baseline, numbers were significantly increased for early and non-specified SCs (enSCs) until up to 0.5 h after exercise (0-5 min: +0.64 [Standardized difference in means], p < 0.001; 6-20 min: +0.42, p < 0.001; 0.5 h: +0.29, p = 0.049), for ESCs until 12-48 h after exercise (0-5 min: +0.66, p < 0.001; 6-20 min: +0.43 p < 0.001; 0.5 h: +0.43, p = 0.002; 1 h: +0.58, p = 0.001; 2 h: +0.50, p = 0.002; 3-8 h: +0.70, p < 0.001; 12-48 h: +0.38, p = 0.003) and for HSCs at 0-5 min (+ 0.47, p < 0.001) and at 3 h after exercise (+ 0.68, p < 0.001). Sex, intensity and duration of the intervention had generally no influence. The extent and kinetics of the exercise-induced mobilization of SCs differ between SC-subpopulations. However, also definitions of SC-subpopulations are non-uniform. Therefore, finding a consensus with a clear definition of cell surface markers defining ESCs, HSCs and MSCs is a first prerequisite for understanding this important topic.
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  • 文章类型: Journal Article
    OBJECTIVE: Neurological complications occur at a high frequency after hematopoietic cell transplantation (HCT). However, an absence is noted in the published literature as regards the quantification of the exact burden and the outcomes thereof. In this systematic review, we endeavored to detail if the recipients of HCT developed any noninfectious neurological events/complications.
    METHODS: According to the PICO criteria, medical literature was searched. Complications that were evaluated included: stroke, peripheral neuropathy, myasthenia gravis, seizures, and posterior reversible encephalopathy syndrome. After strictly defining relevant variables and parameters, data from 173 eligible articles were then extracted accordingly, from the full text for each, for quantitative analysis; additionally, two American Society of Hematology conference abstracts were also subject to data extraction.
    RESULTS: As is evident from the results of the data analysis, an increased frequency of these complications was seen in the HCT recipient population in comparison to the general population. The relative risk ranged from 1.33× to 142× depending on the complication studied.
    CONCLUSIONS: These findings demonstrate that the recipients of HCT had a significantly higher risk of neurological complications and that their early recognition can enhance the monitoring of HCT survivors for the early developmental signs of neurological toxicity. This would facilitate timely interventions, thus ensuring a better quality of life.
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  • 文章类型: Journal Article
    Much research has been performed over the last decade on stem cell therapy as treatment for patients with inflammatory bowel disease. Hematopoietic and mesenchymal stem cells, both allogeneic (from someone else) and autologous (from own patient), have been studied with safe and efficacious results in the majority of patients treated for luminal, perianal, and/or fistulizing disease. Here in this review, we highlight all human trials that have been conducted utilizing stem cell therapy treatment in patients with inflammatory bowel disease.
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  • 文章类型: Journal Article
    In vitro generation of red blood cells (RBCs) has the potential to circumvent the shortfalls in global demand for blood for transfusion applications. The conventional approach for RBC generation has been from differentiation of hematopoietic stem cells (HSCs) derived from cord blood, adult bone marrow or peripheral blood. More recently, RBCs have been generated from human induced pluripotent stem cells (hiPSCs) as well as from immortalized adult erythroid progenitors. In this review, we highlight the recent advances to RBC generation from these different approaches and discuss the challenges and new strategies that can potentially make large-scale in vitro generation of RBCs a feasible approach.
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  • 文章类型: Journal Article
    Cytogenetic analysis is essential for the diagnosis and prognosis of hematopoietic neoplasms in current clinical practice. Many hematopoietic malignancies are characterized by structural chromosomal abnormalities such as specific translocations, inversions, deletions and/or numerical abnormalities that can be identified by karyotype analysis or fluorescence in situ hybridization (FISH) studies. Single nucleotide polymorphism (SNP) arrays offer high-resolution identification of copy number variants (CNVs) and acquired copy-neutral loss of heterozygosity (LOH)/uniparental disomy (UPD) that are usually not identifiable by conventional cytogenetic analysis and FISH studies. As a result, SNP arrays have been increasingly applied to hematopoietic neoplasms to search for clinically-significant genetic abnormalities. A large numbers of CNVs and UPDs have been identified in a variety of hematopoietic neoplasms. CNVs detected by SNP array in some hematopoietic neoplasms are of prognostic significance. A few specific genes in the affected regions have been implicated in the pathogenesis and may be the targets for specific therapeutic agents in the future. In this review, we summarize the current findings of application of SNP arrays in a variety of hematopoietic malignancies with an emphasis on the clinically significant genetic variants.
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  • 文章类型: Case Reports
    OBJECTIVE: Myeloid and lymphoid neoplasms with abnormalities of fibroblast growth factor receptor 1 gene (FGFR1) are a rare and aggressive disease group that harbors translocations of FGFR1 with at least 14 recognized partner genes. We report a case of a patient with a novel t(17;21)(p13;q22) with RUNX1 rearrangement and trilineage blasts.
    METHODS: A 29-year-old man with relapsed T-lymphoblastic lymphoma in the cervical nodes showed a myeloproliferative neoplasm in his bone marrow with three separate populations of immunophenotypically aberrant myeloid, T-lymphoid, and B-lymphoid blasts by flow cytometry. Cytogenetic and fluorescent in situ hybridization studies showed unique dual translocations of t(8;13)(p11.2;q12) and t(17;21)(p13;q22) with RUNX1 rearrangement.
    RESULTS: The patient was initiated on a mitoxantrone, etoposide, and cytarabine chemotherapy regimen and died of complications of disease 1 month later.
    CONCLUSIONS: To our knowledge, this is the first reported case of a myeloid and lymphoid neoplasm with abnormalities of FGFR1 with t(17;21)(p13;q22) and trilineage blasts.
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