胎肝基质细胞强化骨髓移植治疗急性放射病

目的为进一步提高骨髓移植效果。方法以昆明种小鼠急性放射病为模型，进行了胎肝基质细胞强化同种异基因骨髓移植，观察了小鼠造血重建、急性移植物抗宿主病（ＧＶＨＤ）及小鼠存活率。结果胎肝基质细胞移植可强化骨髓移植效果，与单纯骨髓移植组比较，于照射后第１１天小鼠外周血白细胞、骨髓有核细胞计数，ＣＦＵ－Ｅ、ＣＦＵ－ＧＭ、ＣＦＵ－Ｆ、ＣＦＵ－Ｓ回升较快，ＣＦＵ－Ｆ已达正常，于照射后第１７天造血得以重建；ＧＶＨＤ较轻，存活率显著提高，达６０％。结论胎肝基质细胞改善了造血微环境，可能既改善了“龛位”，又增加了“龛位”使干细胞更多的植入，促进了造血重建，提高了骨髓移植效果，是一种“种子与土壤”并重的移植新方法。     

骨髓细胞经酸性成纤维细胞生长因子孵育后程序移植 …

目的 充分利用酸性成纤维细胞生长因子促进血重建的作用，以进一步完善程序移植新方法。方法 以昆明种小鼠急性放射病为模型，进行了骨髓细胞（ＢＭＣ）经自牛脑中制备的ａＦＧＦ卵育后程序移植对造血重建、急性移植物抗宿生病（ＧＶＨＤ）的研究。     

小鼠骨髓细胞及骨髓基质细胞混合输注对骨髓移植后造血重建的影响

观察小鼠骨髓细胞及骨髓基质细胞混合输注对骨髓移植后造血重建的影响。给予受致死剂量照射的Ｂａｌｂ／ｃ小鼠输注同基因骨髓细胞１×１０７ 个及经体外扩增的同基因原代骨髓基质细胞 ２×１０５ 个,与单纯骨髓移植组比较,移植后第１４ 天外周血白细胞、血小板回升较快,第１５ 天、第２０ 天ＢＦＵ－ＧＭ、ＢＦＵ－Ｅ、ＣＦＵ－Ｅ、ＣＦＵ－Ｓ明显高于后者,第２０ 天已达正常。　结论：原代骨髓基质细胞不仅是可以移植的,而且能够加快造血重建,提高移植效果。     

异基因骨髓移植供者使用粒细胞集落刺激因子对骨髓重建与移植物抗宿主病的影响

异基因外周血干细胞移植，具有造血重建快，粒细胞缺乏和血小板减少期缩短，增加了移植期的安全性，由于输入Ｔ淋巴细胞数量较多，可能增加移植物抗宿主病（ｇｒａｆｔｖｅｒｓｕｓｈｏｓｔｄｉｓｅａｓｅ，ＧＶＨＤ）的发病率，特别是慢性ＧＶＨＤ［１］。在小鼠不相合的骨髓移植实验研究，提前使用粒细胞集落刺激因子（Ｇ－ＣＳＦ）动员供者骨髓，移植后降低了重症ＧＶＨＤ的发生，提高了生存率［２］。在自体骨髓移植中，加用少量外周血干细胞，可加速造血重建［３］。本文在ＨＬＡ相合的异基因骨髓移植中，提前给供者使用（Ｇ－ＣＳＦ）…     

粒细胞集落刺激因子对骨髓移植及外周血祖细胞保护的骨髓造血重建

１１ 例急性白血病及中－ 高恶性度非何杰金氏淋巴瘤患者，采用自体／异基因骨髓移植和外周血造血祖细胞保护的大剂量化疗。骨髓或外周血造血祖细胞回输后，开始使用Ｇ－ ＣＳＦ ２．５－ ５ μｇ／ｋｇ，１／日。Ｇ－ＣＳＦ使用天数分别为：外周血造血祖细胞保护组１１±２ ｄ；自体骨髓移植组１８±２ ｄ；异基因骨髓移植组２０±２ ｄ。骨髓涂片显示：骨髓增生活跃。外周血象恢复时间缩短，骨髓及外周血ＣＦＵ－ＧＭ ，ＢＦＵ－Ｅ， ＣＦＵ －ｍ ｉｘ 培养和ＣＤ３４＋ ＣＤ３８＋ 、ＣＤ３４＋ ＣＤ３８－ 细胞检测表明造血祖细胞恢复良好。Ｇ－ＣＳＦ能促进骨髓造血重建，缩短骨髓空虚期，减少严重感染的发生     

混合骨髓移植后短期IL-2治疗增强移植物抗白血病效应的实验研究

目的：增强混合骨髓移植（ＭＢＭＴ）后移植物抗白血病（ＧＶＬ）效应，减少ＭＢＭＴ后白血病的复发率。方法：研究了同基因骨髓混合Ｈ２半相合异基因骨髓移植后腹腔短期注射白介素２（ＩＬ２）对Ｐ３８８小鼠白血病生存的影响。结果：ＭＢＭＴ后白血病小鼠的生存较同基因ＢＭＴ者显著延长，而ＭＢＭＴ＋ＩＬ２治疗组的生存率又显著较ＭＢＭＴ组高，所有小鼠临床皆未发生明显ＧＶＨＤ。结论：ＭＢＭＴ后短期ＩＬ２治疗能显著提高ＧＶＬ效应，为临床治疗恶性血液病提供了新的途径     

OSTEOGENIC POTENTIAL OF RABBIT DERMAL FIBROBLASTS CULTURED IN VITRO: A HISTOCHEMICAL AND RADIOAUTO-GRAPHICAL STUDY

ＯＳＴＥＯＧＥＮＩＣＰＯＴＥＮＴＩＡＬＯＦＲＡＢＢＩＴＤＥＲＭＡＬＦＩＢＲＯＢＬＡＳＴＳＣＵＬＴＵＲＥＤＩＮＶＩＴＲＯ：ＡＨＩＳＴＯＣＨＥＭＩＣＡＬＡＮＤＲＡＤＩＯＡＵＴＯ┐ＧＲＡＰＨＩＣＡＬＳＴＵＤＹＣＨＡＩＢｅｎ－ｆｕ（柴本甫），ＴＡＮＧＸｕｅ－...     

HLA配型相合母子间移植1例

本文报告了１例母子间外周血干细胞移植病例。供受者ＨＬＡ表型完全相合．但供者ＣＭＶ—ＩｇＧ（＋）,ＩｇＭ（＋）。预处理为全身照射（ＴＢＩ）加环磷酰胺（ＣＹ）方案,环孢素Ａ（ＣＳＡ）加甲氨喋呤（ＭＴＸ）方案预防ＧＶＨＤ。输入ＭＮＣ ３．３×１０３／ｋｇ,ＣＤ３４＋ＣＤ３８—１１．８×１０６／ｋｇ。ＷＢＣ下降到最低点（０．１×１０９／Ｌ）为移植后第７天,血小板下降到最低点（７×１０９／Ｌ）为第８天。ＷＢＣ超过１．０×１０９／Ｌ为第１９天,血小板达到２０×１０９／Ｌ上下为第２５天。移植后第３０天、５８天两次行细胞遗传学检查,结果均为４６（Ｘ,Ｘ）。移植后产生了ＩＶ度ａＧＶＨＤ和ＣＭＶ间质性肺炎,经积极治疗后均得到控制。移植后已近２年,现血象基本正常,有局限性ｃＧＶＨＤ表现。仍在服用环胞素Ａ胶囊中。本文对二代间移植的相关问题进行了讨论。     

Effects of Level Changes of 5-HT and Dopamine in Cerebral Microvasculature on Occurrence of Secondary Damages in Traumatic Brain Injury in Rats

ＥＦＦＥＣＴＳＯＦＬＥＶＥＬＣＨＡＮＧＥＳＯＦ５┐ＨＴＡＮＤＤＯＰＡＭＩＮＥＩＮＣＥＲＥ┐ＢＲＡＬＭＩＣＲＯＶＡＳＣＵＬＡＴＵＲＥＯＮＯＣＣＵＲＲＥＮＣＥＯＦＳＥＣＯＮＤＡＲＹＤＡＭＡＧＥＳＩＮＴＲＡＵＭＡＴＩＣＢＲＡＩＮＩＮＪＵＲＹＩＮＲＡＴＳＫＥ...     

AN EVALUATION OF THE EFFECT OF LARGE DOSE OF DEXAM-ETHASONE ON POSTOPERATIVE BRAIN EDEMA IN PATIENTS WITH SEVERE HEAD INJURY

ＡＮＥＶＡＬＵＡＴＩＯＮＯＦＴＨＥＥＦＦＥＣＴＯＦＬＡＲＧＥＤＯＳＥＯＦＤＥＸＡＭ┐ＥＴＨＡＳＯＮＥＯＮＰＯＳＴＯＰＥＲＡＴＩＶＥＢＲＡＩＮＥＤＥＭＡＩＮＰＡＴＩＥＮＴＳＷＩＴＨＳＥＶＥＲＥＨＥＡＤＩＮＪＵＲＹＺＨＵＣｈｅｎｇ（朱诚），ＺＨＡＮＧＧｕ...     

IL-3和IL-6单独和联合IL-1, G-CSF, GM-CSF对小鼠异基因骨髓移植后血小板计数的影响

我们在一个小鼠异基因骨髓移植模型中检测ＩＬ－３和ＩＬ－６单独和联合ＩＬ－１，Ｇ－ＣＳＦ，ＧＭ－ＣＳＦ对血小板恢复的影响。当单独给予时，与正常对照小鼠比较（２１６×１０９／Ｌ），ＩＬ－６和Ｇ－ＣＳＦ分别显著增加移植后６天血小板计数（３１２×１０９／Ｌ，Ｐ＜０．０５；３０９×１０９／Ｌ，Ｐ＜０．０１）。ＩＬ－３单独给予血小板计数为３０３×１０９／Ｌ，（Ｐ＜０．０５）。在联合给予中，只有ＩＬ－３＋Ｇ－ＣＳＦ显著增加移植后６天血小板计数（３２８×１０９／Ｌ，Ｐ＜０．０５）。     

脐带血造血干细胞的“质”“量”研究

目的 对脐带血造血干细胞移植的“质”“量”作出评估，使其更广泛有效地应用于临床。 方法 利用免疫磁珠分离法、ＦＡＣＳ分析与分选、体外液体培养，铺展贴壁等方法对脐带血ＣＤ３４＾＋造血干、粗细胞及其的数量、体外增殖分化性能、生长因子扩增效应，植入成人骨髓基质效率等进行研究，数据经ｔ检验。结果 脐带血有核细胞、ＣＦＣｓ、ＣＤ３４＾＋细胞及其亚群等的绝对数量明显低于常规骨髓移植所需的细胞数量，但脐带血ＣＤ     

103Pd放射性支架持续照射犬胆管的放射性损伤的实验研究

目的　寻找动物胆管金属内支架植入方法 ,观察动物胆管植入1 0 3 Pd放射性支架 ,胆管腔内照射的放射性损伤。方法　实验动物为雄性健康杂种犬 ,体重 1 5～ 2 0kg。麻醉下经手术植入1 0 3 Pd放射性金属支架于犬的胆管腔内 ,1 0 3 Pd的放射性活度分别为 1 2 5× 1 0 4kBq、1 6 6× 1 0 4kBq、2 2 2× 1 0 4kBq、2 5 9× 1 0 4kBq、2 9 6× 1 0 4kBq和 3 7× 1 0 5kBq ,植入后 30d取出1 0 3 Pd放射性金属支架和胆管 ,后者经组织切片HE染色 ,光镜下进行放射性损伤的评价。结果　放射性活度为 1 2 5× 1 0 4kBq ,光镜下可观察到黏膜损伤 ;放射性活度为 2 2 2× 1 0 4kBq时胆管放射性损伤达肌层 ;放射性活度为3 7× 1 0 5kBq时放射性损伤达胆管壁外膜 ,出现胆管穿孔。根据不同放射性活度照射后 ,胆管的放射性损伤的放射性活度效应曲线得出 ,ED50 为 2 8 2× 1 0 4kBq。结论　1 0 3 Pd金属支架胆管腔内近距离照射有明显的剂量 效应关系 ,为该放射性支架应用于临床治疗胆管良、恶性狭窄提供重要的实验依据     

Engraftment of bone marrow-derived cells after nonlethal radiation in syngeneic C57BL/6 mice

Objective To study the characteristics of cell engraftment in mice at a lower dose under nonlethal radiated condition.Methods A syngeneic C57BL/6 mouse model,transplanted with 1 × 107 bone marrow cells...     

Second allogenic bone marrow transplantation after late graft rejection in a patient with severe aplastic anemia

Allogeneic bone marrow transplantation (BMT) is the treatment of choice in young patients (pts) with severe aplastic anemia (SAA) who have an HLA identical sibling donor. Late graft rejection to following allogeneic BMT for SAA is a significant clinical problem and is associated with a high risk of mortality. The optimal treatment strategy for patients with late graft rejection after first BMT is still an open question. We report 12-year-old patient with acquired SAA who underwent BMT from his HLA identical sister. BMT was first-line treatment within 3 months of diagnosis. Preparative therapy was Cyclophosphamide (Cy) 200 mg/kg body mass (BM) during 4 days. Graft versus host disease (GVHD) was prevented with Methotrexate (MTX), Methylprednisolone (MPDN) and Cyclosporin A (CsA). After 17 months, during which patient was with normal blood counts and full donor chimaerism, graft rejection occurred. The patient was re-engrafted from the same donor after conditioning with Cy 200 mg/kg BM plus horse antithymocyte globulin (ATG)--2 vials (á 25 mg)/10 kg BM over 4 days. Before the collection, donor's bone marrow was activated with low dose rhGM-CSF (3 micrograms/kg one day). Following a secondary BMT engraftment has sustained. The patient is alive with full donor chimaerism 26 months from secondary transplantation, without acute or chronic GVHD.     

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models

Purpose:?Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined.

Materials and methods:?In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices (⁶⁰Cobalt; ¹³⁷Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically.

Results:?Acute GvHD was induced by a dose rate of 0.85 Gy/min (⁶⁰Cobalt) and a total dose of 9 Gy and injection of 5×10⁵ lymph node cells plus 5×10⁶ bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with ¹³⁷Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD.

Conclusions:?Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.     

Attenuation of radiation-induced gastrointestinal damage by epidermal growth factor and bone marrow transplantation in mice

Purpose: We examined the effect of epidermal growth factor (EGF) and bone marrow transplantation (BMT) on gastrointestinal damage after high-dose irradiation of mice.

Material and methods: C57Black/6 mice were used. Two survival experiments were performed (12 and 13 Gy; ⁶⁰Co, 0.59–0.57 Gy/min). To evaluate BMT and EGF action, five groups were established – 0 Gy, 13 Gy, 13 Gy + EGF (at 2 mg/kg, first dose 24 h after irradiation and then every 48 h), 13 Gy + BMT (5 × 10⁶ cells from green fluorescent protein [GFP] syngenic mice, 4 h after irradiation), and 13 Gy + BMT + EGF. Survival data, blood cell counts, gastrointestine and liver parameters and GFP positive cell migration were measured.

Results: BMT and EGF (three doses, at 2 mg/kg, administered 1, 3 and 5 days after irradiation) significantly increased survival (13 Gy). In blood, progressive cytopenia was observed with BMT, EGF or their combination having no improving effect early after irradiation. In gastrointestinal system, BMT, EGF and their combination attenuated radiation-induced atrophy and increased regeneration during first week after irradiation with the combination being most effective. Signs of systemic inflammatory reaction were observed 30 days after irradiation.

Conclusions: Our data indicate that BMT together with EGF is a promising strategy in the treatment of high-dose whole-body irradiation damage.     

低剂量全身照射在非清髓性干细胞移植中的临床研究

目的 观察非清髓性低剂量全身照射的临床效果和急性毒副作用。方法 2006年1月至2008年1月对27例异基因造血干细胞移植患者采用含有全身照射的非清髓预处理方案:全身照射(TBI)2 Gy,一次完成;受者原发病不同,受者机体状态、年龄、脏器功能以及供受者HAL相合情况等不同,使用的化疗方案也有不同,包括氟达拉宾、环磷酰胺、阿糖胞苷、马法兰等。预防移植物抗宿主病(GVHD)采用:环孢霉素、霉酚酸酯。结果 造血重建情况: 27例均于移植后第4~8天外周血WBC降至(0.05~0.9)×10⁹/L。中性粒细胞计数>0.5×10⁹/L为8~22 d(中位数为10.5 d),血小板计数>30×10⁹/L为11~28 d(中位数为14.5 d)。1、2年生存率为85.2%(23/27)、77.8%(21/27)。发热率65%,10例发生感染。无出血性膀胱炎和肝静脉闭塞症等并发症。急性GVHD 4例(15%), 慢性GVHD 5例(19%)。随访3~22个月21例(77.8%)仍存活。结论 采用低剂量全身照射的非清髓性造血干细胞移植预处理方案简便安全,并发症少,适应证广;全身照射总剂量2 Gy,1次完成的方案是安全有效的,可以达到免疫抑制效果。     

Non-invasive tracking of human haemopoietic CD34+ stem cells in vivo in immunodeficient mice by using magnetic resonance imaging

Objective

To assess migration of CD34⁺ human stem cells to the bone marrow of athymic mice by using magnetic resonance (MR) imaging and Resovist, a contrast agent containing superparamagnetic iron oxide (SPIO) particles.

Methods

All animal and human procedures were approved by our institution’s ethics committee, and women had given consent to donate umbilical cord blood (UCB). Balb/c-AnN Foxn1^nu/Crl mice received intravenous injection of 1?×?10⁶ (n?=?3), 5?×?10⁶ (n?=?3) or 1?×?10⁷ (n?=?3) human Resovist-labelled CD34⁺ cells; control mice received Resovist (n?=?3). MR imaging was performed before, 2 and 24 h after transplantation. Signal intensities of liver, muscle and bone marrow were measured and analysed by ANOVA and post hoc Student’s t tests. MR imaging data were verified by histological and immunological detection of both human cell surface markers and carboxydextran-coating of the contrast agent.

Results

CD34⁺ cells were efficiently labelled by Resovist without impairment of functionality. Twenty-four hours after administration of labelled cells, MR imaging revealed a significant signal decline in the bone marrow, and histological and immunological analyses confirmed the presence of transplanted human CD34⁺ cells.

Conclusion

Intravenously administered Resovist-labelled CD34⁺ cells home to bone marrow of mice. Homing can be tracked in vivo by using clinical 1.5-T MR imaging technology.