HUMAN-MOUSE CHIMERA ASSAYS

淋巴造血干/祖细胞生物学是长期关注的对象 西文博士的实验室。另外，作为临床血液学家- 肿瘤学家，我们希望将我们的工作直接应用于临床 治疗，特别是干细胞/祖细胞移植。进一步 了解人类干细胞/祖细胞的生物学是必不可少的。 对于许多与临床相关的基本问题，因为这些是 重型再生障碍性贫血(SAA)、骨髓增生异常的起源细胞 综合征(MDS)和白血病，以及因为纯化的干细胞/祖细胞 是强大的治疗工具，特别是(尽管不是唯一的) 血液系统疾病。 可行的人淋巴造血实验室检测方法的建立 干细胞(HSC)是重要的基础知识的造血和 用于临床骨髓移植。新的HSC检测方法必须经过临床验证 候选造血干细胞的移植，因为人类移植目前 唯一能确凿证明移植物中存在人类HSC的方法。 项目2的具体目标1将广泛地描述“SCID” “重新填充细胞”(SRC)，即正常的人类造血细胞 在受辐射的免疫缺陷小鼠中移植，关于 免疫表型。将SRC与正常人和小鼠HSC进行比较。 具体目标2将确定短期体外培养的效果， SRC是造血移植的重要途径。特定的 目标3将评估SRC分析在SAA、MDS、白血病、 和儿科实体瘤。这可能会对癌症有更好的定义 干细胞，导致复发的细胞。黄曲霉毒素的实验室研究 项目2中的正常和恶性干细胞/祖细胞生物学是中心 到整个计划项目。

Lymphohematopoietic stem/progenitor cell biology is the long-term interest of Dr. Civin's laboratory. In addition, as clinical hematologist- oncologists, we desire to make direct application of our work to clinical treatment, especially stem/progenitor cell transplantation. Further understanding of the biology of human stem/progenitor cells is essential for many basic questions with clinical relevance, since these are the cells of origin of severe aplastic anemias (SAA), myelodysplastic syndromes (MDS) and leukemias, and because purified stem/progenitor cells are powerful therapeutic tools, especially (though not exclusively) for hematologic disorders. Development for feasible laboratory assays for human lymphohematopoietic stem cells (HSC) is important for basic understanding of hematopoiesis and for clinical BMT. New assays for HSC must be validated by clinical transplantation of candidate HSC, since human transplantation is currently the only way to definitively prove the presence of human HSC in the graft. Specific Aim 1 of Project 2 will extensively characterize "SCID repopulating cells" (SRC), the normal human hematopoietic cells which engraft in irradiated immunodeficient mice, with respect to immunophenotype. SRC will be compared with normal human and murine HSC. Specific Aim 2 will determine the effects of short-term ex vivo culture, an important approach in hematopoietic transplantation, on SRC. Specific Aim 3 will assess the use of SRC assays in cases of SAA, MDS, leukemias, and pediatric solid tumors. This may allow better definition of cancer stem cells, the cells which cause relapse. The laboratory investigation of normal and malignant stem/progenitor cell biology in Project 2 is central to the entire Program Project.