STEM CELL DIFFERENTIATION & BONE MARROW TRANSPLANTATION

干细胞分化

• 批准号: 3239385
• 负责人: STEPHEN G EMERSON
• 金额: $ 15.53万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3239385
• 关键词: antibody dependent killer cell; bone marrow transplantation; cell adhesion; cell cell interaction; cell differentiation; cell population study; cell type; colony stimulating factor; endonuclease; erythropoietin; fibroblasts; gel electrophoresis; genotype; glycoproteins; graft versus host disease; helper T lymphocyte; hematopoiesis; hematopoietic growth factor; hematopoietic stem cells; histocompatibility typing; human subject; immunogenetics; immunohematology; leukocyte activation /transformation; macrophage; messenger RNA; monoclonal antibody; nucleic acid hybridization; radioimmunoassay; suppressor T lymphocyte; tissue /cell culture

We will utilize the setting of bone marrow transplantation to study stem cell and progenitor differentiation by characterizing in detail the regulation of hematopoiesis following transplantation, and in particular will examine the role of granulocyte-monocyte- colony stimulating factor (GM-CSF) in engraftment. The bone marrow transplant patient provides a unique and important setting for studying the regulation of hematopoiesis. Unlike studies of adult bone marrow which reflect the expression of committed progenitors which have developed in a steady state, experiments with regenerating bone marrow post-transplantation can illuminate the control of the development of these progenitors from pluripotent stem cells. Information obtained from these studies may have direct relevance to the clinical success of the transplantation procedure, particularly those involving haploidentical transplants and T cell depletion of donor marrow. Specific aims will be to: 1. Analyze the progenitor-adventitial cell interactions in the bone marrow transplant recipients. Measure the extent of defects in hematopoietic helper cell function in these patients. 2. Measure GM-CSF expression and production in hematopoietic helper cell fractions to determine the cause of helper cell defects. 3. Determine the genotype of functional helper cell subsets in recipient marrow samples. 4. Study the influence on in vitro colony growth of specific peripheral blood lymphoid populations and their soluble growth factors such as GM-CSF that develop posttransplantation, notably from patients undergoing graft-versus-host disease, delayed engraftment, or impending graft rejection. 5. Determine the roles of accessory cells, growth factors, and genetic identity in stem cell differentiation on an in vitro monolayer of stromal ST.1 fibroblasts. These studies will utilize the bone marrow transplant setting to analyze the interactions between hematopoietic stem cells and surrounding cells in hematopoietic differentiation. Through these experiments we hope to illuminate the control of hematopoiesis and to improve our understanding of engraftment in clinical bone marrow transplantation. We hope that our findings will help us to modify this important procedure so as to encourage rapid engraftment without the onset of graft-versus-host disease.

我们将利用骨髓移植的设置来 通过研究干细胞和祖细胞分化的特性 详述移植后的造血调控， 尤其是将研究粒细胞-单核细胞的作用- 移植中的集落刺激因子(GM-CSF)。这块骨头 骨髓移植患者提供了一个独特而重要的环境 用于研究造血的调节作用。不同于对 哪些成人骨髓反映了承诺的表达 在稳定状态下发育的祖细胞，实验 移植后再生的骨髓可以 说明对这些祖细胞发育的控制 来自多能干细胞。从这些网站获得的信息 研究可能与临床上的成功有直接关系 移植程序，特别是涉及 单倍体相合移植与供者骨髓T细胞耗竭 具体目标将是： 1.分析外膜细胞与祖细胞的相互作用。 骨髓移植受者。测量缺陷的程度 在这些患者的造血辅助细胞功能方面。 2.检测GM-CSF在造血细胞中的表达和产生 辅助细胞分数以确定辅助细胞的原因 缺陷。 3.确定儿童功能性辅助性细胞亚群的基因 受者骨髓样本。 4.研究不同菌落生长对特定菌落生长的影响。 外周血淋巴组织及其可溶性生长 移植后发生GM-CSF等因素值得注意 来自正在接受移植物抗宿主病的患者，延迟 植入，或即将发生的移植排斥反应。 5.确定辅助细胞、生长因子和 干细胞体外分化过程中的遗传同一性 间质ST1成纤维细胞单层。 这些研究将利用骨髓移植环境来 分析造血干细胞与细胞因子的相互作用 周围细胞在造血分化中的作用。通过这些 我们希望通过实验阐明对造血的调控 提高对临床植骨的认识 骨髓移植。我们希望我们的发现将帮助我们 修改这一重要程序，以鼓励快速 无移植物抗宿主病发病的植入术。