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Application of hemopoietic stem cells included hemopoietic stem cell transplantation and as target cells for gene therapy.

造血干细胞的应用包括造血干细胞移植和作为基因治疗的靶细胞。

Objective:To explore the effect of different combination of hematopoietic cell growth factorson expanding umbilical cord blood hemopoietic cells in vitro.

目的:探讨造血细胞生长因子的不同组合对脐血CD34+造血干细胞的扩增作用。

BACKGROUND: At present, hemopoietic stem cells have been proved to differentiate into nerves in rodents animals. As for the human, this topic is in debate.

背景:近年来,在啮齿类动物中发现,造血干细胞具有向神经分化的塑型性,而在人类,这种造血的塑型性仍然具有争议。

In this study, Mono-nuclear cells containing hematopoietic stem/progenitor cells were isolated from umbilical cord blood of normal full-term deliveries, healthy adult and heterocellular HPFH patient bone marrow by density gradient centrifugation. After simple purification and expansion in vitro, MNCs were induced to erythroid cell differentiation using different culture systems and cytokines including Epo, IL-3 and GM-CSF.

本研究首先利用密度梯度离心方法,从正常成人和异细胞型遗传性胎儿血红蛋白持续存在综合症家系患者的骨髓组织、健康足月正常分娩胎儿脐带血中分离得到了含有造血干/祖细胞的单个核细胞(Mono-Nuclear Cell,MNC),进行初步纯化及体外扩增后,组合使用Epo、IL-3、GM-CSF等细胞因子,将造血干/祖细胞向红系方向进行诱导培养。

The transforming growth factor-β superfamily, a large group of highly conserved growth factors including TGF-βs, activins and BMPs, regulate a wide variety of cellular functions such as proliferation, differentiation, apoptosis and migration. Signals from these growth factors are transduced by a group of Smad proteins. To date, there are nine vertebrate Smads, including the receptor-activated Smads , Smadsl-3, 5 and 8, the common mediator Smad4 and Smad4β, and the inhibitory Smads, Smad6 and 7. Signaling is initiated when the ligand induces assembly of a heteromeric complex of type Ⅱ and type Ⅰ TGFβ receptors. Then R-Smads are directly phosphorylated by activated type I TGF-β receptors.

在多种SMADS中,SMAD5令我们产生兴趣,基于三个原因:1、Smad5基因敲除胚胎中发现卵黄囊的异位造血以及CFU-GM祖细胞数目增加,表明SMAD5可能是早期造血发育的负向调控基因。;2、应用反义核酸封闭Smad5可以逆转TGF-β对祖细胞增殖的抑制效应,表明它可能介导TGF-β信号转导,后者的异常,包括某些SMADS的功能异常,和白血病紧密相关;3、Smad5基因定位在人染色体5q21,此区域的缺失和急性髓系白血病和骨髓增生异常综合症相关,因此,Smad5被怀疑为白血病抑制基因。

To appraise effect of the home-made recombinant human granulocyte colony stimulating factor in the mobilization peripheral blood stem cells. From 2001 to 2005, 20 patients undergoing autologous peripheral blood stem cell transplantation were enrolled, 11 males, 9 females, 11 patients with acute myelocytic leukemia, 5 patients with acute lymphocyte leukemia, 3 patients with malignant lymphoma, and 1 patient with multiple myeloma.

为评估国产重组人粒细胞集落刺激因子在动员外周造血干细胞的效果,选择2001/2005收治的20例自体外周血造血干细胞移植患者,男11例,女9例,其中急性髓细胞白血病11例,急性淋巴细胞白血病5例,恶性淋巴瘤3例,多发性骨髓瘤1例。

However, this approach conferred the resistance to not only myelopoietic cells but also tumor cells that have invaded or metastasized into bone marrow or circulating blood for nonspecific expression of the exogenous genes.

详细骨髓造血细胞中导入耐药耐辐射基因是克服放化疗对造血系统抑制作用的有效手段,但外源基因的非特异性表达也增加了残存在血液或者侵犯至骨髓中的肿瘤细胞耐受性。

Of them, malignant hematological disease accounted for 48.3%(52 cases), nonmalignant hematological disease accounted for 37.7%(40 cases), and non hematological disease accounted for 14%(15 cases).

结果:最后确诊造血系统疾病92例(86%),其中恶性血液病52例(48.3%),非恶性血液病40例(37.7%),非造血系统疾病共15例(14 %)。

Megakaryocytes in fetal liver and bone marrow are small sized during ontogenesis and remain so until a few months after delivery .

在胚胎发育时期,无论是胎肝造血还是骨髓造血,巨核细胞形态均较小,直到出生后几个月,仍小于成人的巨核细胞。

The 1〓 generation of which is transfusion with mature cells, such as the whole blood and blood ingredient: the representative of the second generation is hematopoietic stem/progenitor cells transplantation, which can regraft normal hematopoiesis and immunity in a body with destroyed immunity and hematopoiesis by the self-renewal and multiple differentiation capacity of stem cells.

第一代细胞疗法是成熟血细胞的输注,如全血输注及成分输血等,对于纠正各种血细胞减少有明显疗效;第二代细胞疗法的代表是干细胞移植,指利用干细胞能够在体内自我更新和多向分化的能力在病态免疫和造血功能被摧毁的机体内重建正常的造血和免疫功能。

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