CFU-S增殖调控因子的研究概况

本文对调控造血干细胞(CFU-S)增殖状态的一对作用相反因子的组织来源,生成细胞及其生物学作用进行了简略概述.文中还根据初步研究结果分析了这一研究的意义.     

RBE of spleen CFU-S to low dose rate Cf-252 or photon radiation in vivo

The biological effects of low dose rate (LDR) Cf-252 radiation were compared to LDR Cs-137 photon radiation and acute ⁶⁰Co radiation. The RBE_n for endogenous CFU-S in vivo was 2.1 for neutron radiation at a dose rate of 9.9 cGy/hr of Cf-252 radiation. The value was consistent with previous in vitro experiments where a value of 2.1 was found. For the low doses and low dose rates studied, we tested an acute assay dose following the LDR irradiation to determine dose-effect and RBE_n. Organ size shrinkage and regeneration patterns after LDR Cf-252 and Cs-137 were also studied and showed greater growth delay for Cf-252 irradiated lympho-hemopoietic tissues.     

苯甲酸雌二醇对受照射小鼠外源性造血重建的影响

LACA小鼠经⁶⁰Coγ 线致死剂量照射后移植同系骨髓细胞或胎肝细胞,观察肌注0.15mg苯甲酸雌=醇对造血重建的影响。结果表明,不论移植前3天或移植后1天一次用药,对外源性遗血重建均有抑制作用。与移植对照组相比,外周血自细胞,骨髓有核细胞,骨髓CFU-S和CFU-GM—D以及股骨与脾脏的组织学改变均有延迟恢复的趋势,尤以移植后用药更为显著,且加速受体小鼠死亡。     

Effect of adult thymectomy and splenectomy on pluripotent stem cells and progenitors of the myeloid and B-lymphoid lineages

In order to investigate the regulatory interactions which occur between the bone marrow, the thymus and the spleen during hemopoiesis, the numbers of granulo-macrophage and B-lymphocyte precursors (GM-CFC and BL-CFC) and the kinetics of pluripotent stem cells (CFU-S) have been studied in the bone marrow and the spleen of normal adult thymectomized and/or adult splenectomized mice with or without T-dependent antigen stimulation. The results suggest that (1) medullary and splenic CFU-S may be two different populations of the stem cell compartment; (2) the thymus is involved in medullary but not in splenic CFU-S proliferation in response to T-antigen challenge; (3) the spleen influences GM-CFC and BL-CFC numbers and (4) antigenic stimulation modifies medullary BL-CFC.     

小鼠脾集落形成期基质细胞在体外扩增脐带血CD34^＋细胞中的作用

目的：研究来源于小鼠脾脏的基质细胞在体外扩增脐血CD34^ 细胞中的作用;方法：取γ射线照射后小鼠脾集落形成期的脾细胞经人重组单核细胞集落刺激因子（rhM-CSF)的激发培养,获得贴壁脾基质细胞,经丝裂霉素处理后作为滋养细胞,与多种造血细胞生长因子共同应用,体外扩增经免疫磁珠阳性选择法纯化的人脐血CD34^ 细胞,用体外集落形成及流式细胞仪分析扩增细胞的集落形成能力和表型。结果：1）rhM-CSF能有效地刺激小鼠脾基质细胞的生长;2）所获的小鼠脾基质细胞具有支持脐血CD34^ 细胞的集落形成能力,与多种造血细胞生长因子共同应用后,能有效地扩增CD34^ 细胞,扩增2周后的细胞数达100倍,且仍具有多向分化能力。结论：rhM－CSF能刺激小鼠脾集落形成期基质细胞的增殖,该类基质细胞具有有效支持人脐血CD34^ 细胞的体外扩增作用。     

免疫诱导再障小鼠骨髓造血干细胞的改变及机理

作者对给予全身亚致死量照射后的小鼠转输H-2相同、MIS不同的小鼠胸腺淋巴结细胞所诱导的再障模型的造血干细胞进行了观察,结果发现再障小鼠濒死时,造血干细胞极度低下,为0.90±0.83(CFU-S/10~5骨髓有核细胞),与正常组(12.00±1.87)相比有显著性差异(P<0.001),而相应的照射对照组己恢复到8.29±1.98,但仍明显低于正常对照组(P<0.01),输细胞组(11.71±1.16)与正常组无明显差异(P>0.05)。进一步观察发现,照射对照组在处理后第5天造血干细胞处于极低水平,但从第9天起己进入指数性增殖,再障组则一直处于极低水平,直至死亡。再障小鼠的骨髓、胸腺淋巴结、脾细胞对正常造血干细胞有明显的抑制作用,当上述细胞分别以1:1、10:1、10:1与正常骨髓细胞混合转输时,抑制率达62％、83％及93％。     

气血康口服液抗辐射的实验研究

采用内源性脾集落形成法，骨髓有核细胞计数及脾脏称重法观察了气血康口服液对辐射小鼠造血功能的影响。研究结果表明，经气血康处理的小鼠ＣＦＵ－Ｓ、骨髓有核细胞数及脾重等项指标均明显明显高于阴性对照组和阳性对照组，提示气血康口服液在辐射损伤紧急状态下，不仅可促进髓内造血细胞生成，而且对动物体内髓外造血也有显著促进作用。其抗辐射的确切机理有待于进一步研究。     

Regulators of stem cell proliferation in the haemopoietic tissues of W/Wv and SI/SId mice

The presence of CFU-S proliferation stimulatory and inhibitory activities in the bone marrow and spleens of normal mice (+/+) and mice with mutations affecting the proliferative behaviour of stem cells (S1/S1^d and W/W^v) has been investigated.S1/S1^d and +/+ bone marrow and spleen contain virtually no detectable stimulator but the corresponding tissues from W/W^v mice are both strongly stimulatory. SI/SI^d marrow in particular, but also +/+ marrow are strongly inhibitory whilst +/+ spleen, S1/SI^d spleen, W/W^v marrow and W/W^v spleen all contain inhibitory activity but at a lower specific activity.The data are compatible with studies of cell and tissue grafts that have indicated an intrinsic haemopoietic stem cell defect in W/W^v mice and an extrinsic, microenvironmental defect in SI/SI^d mice. It is suggested that they are also compatible with defective regulatory interactions between stem cells and regulator-producing cells and that the W and S1 loci may code for products involved in the production of, or response to, CFU-S proliferation regulators.     

Effects of prolonged nitrous oxide exposure on hemopoietic stem cells in mice

The effects of prolonged exposure to nitrous oxide on the hemopoietic progenitor cells in bone marrow and spleen in mice were investigated. Fifty percent nitrous oxide caused a marked decrease in the number of pluripotent stem cells (CFU-S) and granulocyte-macro-phage progenitor cells (GM-CFC) in the spleen, whereas it caused only a slight decrease in these cells in the bone marrow. These results suggest that prolonged exposure to nitrous oxide induces damage in the splenic hemopoiesis in mice.(Konno M et al.: Effects of prolonged nitrous oxide exposure on hemopoietic stem cells in mice. J Anesth 1: 29–34, 1987)     

Effects of Plutonium-239 on Haemopoiesis. I. Quantitative and Qualitative Changes in CFU-S in Different Regions of the Mouse Femur and Vertebrae

Summary

Mice were injected with plutonium-239 (960 Bq/mouse) and, over a period of four months, the response of haemopoietic tissue and the self-renewal capacity of its stem cells was monitored. Cellularity, CFU-S concentration and self-renewal capacity were measured in five different regions of bone and marrow–axial and marginal marrow of the femoral shaft, femur shaft, proximal and distal ends of the femur shaft and vertebrae.

Cellularities were little affected by plutonium but CFU-S were reduced in all regions, most severely in the bone shaft and marginal marrow due to the initial deposition of plutonium on the bone surface, by four days. The reduction in axial CFU-S, however, was due probably to a relatively long plasma half-life resulting from the tendency of plutonium to combine with plasma proteins. The capacity of CFU-S for self-renewal was reduced and remained low in all zones. Thus, although the highly self-renewing axial CFU-S were depleted, and remained so, due probably to a longer term redistribution of plutonium throughout the marrow, additional proliferation of the more mature CFU-S in the other zones kept their self-renewal low while replenishing their numbers and maintaining a normal cell output.