间充质干细胞在造血干细胞移植中的应用

间充质干细胞(MSCs)是一种具有自我更新和多向分化潜能的成体干细胞,存在于骨髓、脂肪组织、脐血及多种胎儿组织.它可分泌多种细胞因子及生长因子,促进造血干细胞(HSC)的增殖与分化.MSCs还具有免疫调节、抗炎和组织修复作用,可减轻移植物抗宿主病(GVHD)及其他移植相关并发症.     

造血干细胞的研究进展

干细胞研究是一门新兴的学科。经过50多年的努力,造血干细胞的研究已经成为当今生物医学领域中发展最快的领域。介绍了造血干细胞的来源、分离纯化和检测方法以及“可塑性”等方面的研究情况,并详细说明了一些主要的造血干细胞表面标志以及造血干细胞在干细胞移植、细胞治疗和基因治疗等方面的临床应用和前景。     

造血干细胞移植与捐献

造血干细胞移植技术在临床上的应用越来越广泛,是目前白血病等难治性疾病的重要治疗方法之一,给广大患者带来了福音,但目前造血干细胞来源不足制约了其在临床上的广泛应用。介绍了造血干细胞移植与捐献的相关知识,包括造血干细胞移植的种类、临床应用、采集的过程、捐献的流程及捐献对供体的安全性等,旨在提高对造血干细胞捐献的认识。     

造血干细胞移植治疗白血病的护理研究进展

造血干细胞移植（HSCT）是根治白血病的主要手段,治愈率达60％～80％。由于移植过程存在着影响治疗效果的各种负性因素,我们针对移植过程不同阶段负性因素的特点,实施心理支持,并发症的预防、观察与处理,全环境保护方案,健康教育等干预措施,以减轻或消除负性因素对患者的影响,促进患者身心早日康复,提高白血病患者移植后的生活质量。     

造血干细胞移植条件对小鼠造血重建的影响

通过同种基因型小鼠构建造血干细胞移植模型,将预处理的全骨髓单个核细胞或c-Kit⁺造血干细胞移植至致死剂量照射的受体小鼠体内,动态监测移植2～16周后受体小鼠体内供体来源细胞造血重建以及嵌合情况,以期揭示不同群体的供体细胞以及预处理等因素对小鼠造血干细胞移植后造血重建的影响。实验结果显示,移植后早期(2周)全骨髓单个核细胞组髓系比例要高于c-Kit⁺细胞移植组,但全骨髓移植组受体小鼠呈现出较大的移植后不良反应,出现脱毛、食欲不振以及体重减轻的症状。c-Kit⁺细胞移植组在淋系重建上要早于全骨髓移植组,供体细胞的嵌合植入也早于全骨髓移植组,但两组实验组最终均能完成造血重建过程。实验结果表明c-Kit⁺细胞移植组在移植后能够较快地实现供体细胞植入,进而开始造血重建,且c-Kit⁺细胞移植组的不良反应要低于全骨髓移植组。结果说明在整体造血重建效果上c-Kit⁺细胞移植组要优于全骨髓移植组。     

异基因造血干细胞移植中的树突状细胞

树突状细胞(DC)是目前已知的启动免疫反应最强大的抗原呈递细胞(APC),也是惟一能激活初始T细胞的APC。近年来,DC在移植免疫中的作用已成为研究的焦点。简要综述了DC在异基因造血干细胞移植中的研究进展。     

胎肝造血干细胞的移植特性

胚胎发育中,肝脏是一个重要的造血器官。近年来胎肝移植的临床应用重新引起了人们的关注。本文应用染色体的 C-带染色法研究了小鼠骨髓和胎肝造血干细胞在照射受体小鼠中的增殖能力与相互间的竞争作用。实验结果表明胎肝造血干细胞在成年骨髓中的植入率比较同样条件下的成年骨髓造血干细胞低,但胎肝造血干细胞比较成年骨髓造血干细胞具有更强的自我更新或增殖能力。在同种胎肝造血干细胞移植中,为了降低同种移植抗力,提高移植的胎肝造血干细胞在受体中的耐受性,移植前对受体作适当的免疫抑制处理是必要的。因此,克服个体发育屏障和移植免疫屏障是提高同种胎肝造血干细胞移植效果中两个重要的研究课题。     

诱导多能干细胞在血液系统疾病中的研究进展

造血干细胞移植（hemopoietic stem cell transplantation;HSCT）用于血液系统疾病的治疗已取得迅猛发展。但由于供体有限及配型效率不高等问题;严重阻碍了其在临床上的广泛应用。因此;人们迫切地寻求更为安全、经济和有效的造血干细胞的资源。诱导多能干细胞（induced pluripotent stem cells;iPS）在体外可被诱导分化为多种细胞;其中对体外诱导分化为造血干细胞的研究尤为深入。该文就iPS细胞在体外定向分化为造血干细胞及移植研究的最新进展作一综述。     

造血干细胞基因治疗研究进展

近几年来,造血干细胞基因治疗在逆转录病毒载体,动物模型和临床试验等方面取得了明显进行。最近,国外采用该方法临床治理两名SCID－X1患儿获得成功,这是基因治疗单基因疾病领域的一个重大里程碑。     

关于非血缘异基因造血干细胞移植认知程度的调查分析

我国骨髓库的骨髓量远不能满足白血病患者的需求,许多的白血病患者因此延误了治疗时机,丧失了宝贵的生命。本课题的研究通过问卷调查人们对非血缘异基因造血干细胞移植认知程度,根据调查结果分析捐献者缺乏的原因,找到解决方法。     

Intratumoral interferon-α gene transfer enhances tumor immunity after allogeneic hematopoietic stem cell transplantation

One of the major challenges in the treatment of solid cancers by allogenic hematopoietic stem cell transfer (alloHSCT) is the specific enhancement of antitumor immunity. Interferon (IFN) is a cytokine with pleiotropic biological functions including an immunomoduration, and our preclinical studies have shown that an intratumoral IFN-α gene transfer induced strong local tumor control and systemic tumor-specific immunity. In the present study, we examined whether the IFN-α gene transfer could enhance recognition of tumor-associated antigens by donor T cells and augment the antitumor activity of alloHSCT. First, when a mouse IFN-α adenovirus vector (Ad-mIFN) was injected into subcutaneous xenografts of syngeneic renal and colon cancer cells, tumor growth was significantly suppressed in a dose-dependent manner. A significant tumor cell death and infiltration of immune cells was recognized in the Ad-mIFN-injected tumors, and the dendrtic cells isolated from the tumors showed a strong Th1-oriented response. The antitumor effect of Ad-mIFN was then examined in a murine model of minor histocompatibility antigen-mismatched alloHSCT. The intratumoral IFN-α gene transfer caused significant tumor suppression in the alloHSCT recipients, and this suppression was evident not only in the gene-transduced tumors but also in simultaneously inoculated distant tumors which did not receive the vector injection. A cytotoxicity assay showed specific tumor cell lysis by donor T cells responding to IFN-α. Graft-versus-host disease was not exacerbated serologically or clinically in the mice treated with IFN-α. This combination strategy deserves evaluation in future clinical trials for human solid cancers.     

造血干细胞移植治疗白血病患者负性因素干预措施的护理研究

目的针对造血干细胞移植治疗白血病患者不同阶段存在负性因素的特点进行干预并观察其临床效果。方法对96例白血病患者在造血干细胞移植前期-预处理期-移植期-移植后期的不同阶段负性因素实施心理支持,全环境保护方案,并发症的预防、观察与处理,健康教育等干预措施。结果减轻或消除负性因素对患者的影响,减少了并发症的发生,缩短留住无菌层流室的时间,提高白血病患者移植后的生活质量。结论制定一整套合理的、规范的、系统的护理流程,使患者获得最佳护理方案,有效减轻负性因素对患者的影响。     

异基因造血干细胞移植治疗耳道复发的急性早幼粒细胞白血病一例并文献复习

目的:探讨急性早幼粒细胞白血病(APL)髓外复发的相关因素及治疗.方法:对1例APL缓解后耳道复发患者的临床资料进行回顾性分析,并复习相关文献.结果:患者2015年8月诊断为APL(低危型),经诱导后达完全缓解,随后进行巩固、维持治疗,并多次行腰椎穿刺术及椎管内注射化疗药物预防中枢神经系统白血病.2017年3月发现左外...     

细胞的功能冗余性及其意义

引入新概念可能推动学科的发展.近年来冗余性概念已逐步渗入生命科学,细胞因子和转录因子的功能冗余性已引起研究者的关注.但是,对细胞冗余性的研究报道尚少.最近,对成体干细胞可塑性和专职吞噬细胞、兼职吞噬细胞的研究进展引发人们对细胞功能冗余性的思索.综述对细胞冗余性和抗冗余性的有关资料,试从生物医学角度探讨细胞冗余性的作用和意义,建议积极开展对细胞冗余性的研究.     

Gene expression profile of cytokines in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with reduced conditioning

There are no reliable markers useful to predict the onset or the evolution of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT), although several candidate biomarkers have been identified from limited hypothesis-driven studies. In this study we evaluated 14 patients who received a reduced intensity conditioning HSCT. Seven patients had cGVHD, whereas 7 never developed cGVHD during the period of observation. The expression of 114 cytokines in immunoselected cell populations was explored by microarray analysis and 11 cytokines were selected for further evaluation by real-time PCR. Differential gene expression measurements showed a significant up-regulation for INFγ (interferon, gamma) in CD8+ and for TNFSF3 (tumor necrosis factor superfamily, member 3) and for TNFSF10 (tumor necrosis factor superfamily, member 10) in CD14+ cell population when comparing cGVHD with control samples. The expression levels were significantly decreased for TNFSF10 in CD8+ cell population and for TNFSF12 (tumor necrosis factor superfamily, member 12) and for PDGFβ (platelet-derived growth factor, beta) in CD4+. Our data seem to suggest that different immune populations can play a role in cGVHD pathogenesis and the early detection of gene expression profile in these patients could be useful in the monitoring of GVHD. We hypothesized that PDGFβ down-regulation could represent a negative feedback to compensate for enhanced expression of its receptor recently reported.     

造血干细胞移植术对肠道菌群结构的影响

目的监测造血干细胞移植术（Hematopoietic stem cell transplantation,HSCT）前后肠道菌群结构的动态变化。方法收集3例造血干细胞移植患者手术前后8个时间点的粪便样品,提取样品总DNA进行16S rRNA基因的V3区的bar coded 454焦磷酸测序,并用MANOVA、聚类分析、Pearson相关等统计方法对菌群结构的变化进行动态分析。结果 HSCT移植前,经过放、化疗及预防性抗生素治疗,患者的肠道菌群结构和组成发生显著的改变,多样性明显减少;移植4周后,菌群多样性有恢复的趋势,但菌群结构和组成与治疗前仍有明显的差异。整个HSCT过程中,Escherichia/Shigella及Enterococcus属变成肠道中最优势的细菌类群。结论肠道菌群结构在HSCT术前已发生显著的改变,机会致病菌Escherichia/Shigella及Enterococcus属成为HSCT患者肠道中最优势的细菌类群。     

Prospective study on dosimetric comparison of helical tomotherapy and 3DCRT for craniospinal irradiation – A single institution experience

Aim

This prospective study aims to assess feasibility of helical tomotherapy (HT) for craniospinal irradiation (CSI) and perform dosimetric comparison of treatment plans for both HT and 3D conformal radiotherapy (3DCRT).

Background

CSI is a challenging procedure. Large PTV size requires field matching due to technical limitations of standard linear accelerators, which cannot irradiate such volumes as a single field. HT could help to avoid these limitations as irradiation of long fields is possible without field matching.

Materials and methods

Three adults were enrolled from 2009 to 2010. All patients received radiochemotherapy. Treatment plans in prone position for 3DCRT and in supine position for HT were generated. The superior plan was used for patients’ irradiation. Plans were compared with the application of DVH, Dx parameters – where x represents a percentage of the structure volume receiving a normalized dose and homogeneity index (HI).

Results

All patients received HT irradiation. The treatment was well tolerated. The HT plans resulted in a better dose coverage and uniformity in the PTV: HI were 5.4, 7.8, 6.8 for HT vs. 10.3, 6.6, 10.4 for 3DCRT. For most organs at risk (OARs), the D(V80) was higher for HT than for 3DCRT, whereas D(V5) was lower for HT.

Conclusions

HT is feasible for CSI, and in comparison with 3DCRT it improves PTV coverage. HT reduces high dose volumes of OARs, but larger volumes of normal tissue receive low radiation dose. HT requires further study to establish correlations between dosimetrical findings and clinical outcomes, especially with regard to late sequelae of treatment.