STEM CELL DIFFERENTIATION & BONE MARROW TRANSPLANTATION

我们将利用骨髓移植的环境， 研究干细胞和祖细胞分化， 详述了移植后造血的调节， 特别是将检查粒细胞-单核细胞- 集落刺激因子（GM-CSF）。 骨 骨髓移植患者提供了一个独特而重要的环境， 来研究造血的调节。 与研究不同， 成人骨髓中的表达，反映了承诺 在稳定状态下发育的祖细胞，实验 移植后再生骨髓可以 阐明了对这些祖细胞发育的控制 从多能干细胞。 从这些来源获得的信息 研究可能与临床成功直接相关， 移植手术，特别是那些涉及 单倍体相合移植和供体骨髓的T细胞耗竭。 具体目标是： 1. 分析在细胞外基质中祖细胞-外膜细胞的相互作用， 骨髓移植患者 测量缺陷的程度 造血辅助细胞的功能。 2. 测量造血细胞中GM-CSF的表达和产生 辅助细胞组分，以确定辅助细胞的原因 缺陷 3. 确定功能性辅助细胞亚群的基因型 接受者的骨髓样本 4. 研究特异性大肠杆菌对体外菌落生长的影响 外周血淋巴细胞群及其可溶性生长 如GM-CSF的因素，发展移植后，特别是 移植物抗宿主病患者，延迟 移植或即将发生的移植物排斥。 5. 确定辅助细胞、生长因子和 干细胞分化中的遗传同一性 基质ST. 1成纤维细胞单层。 这些研究将利用骨髓移植环境， 分析造血干细胞与 周围细胞的造血分化。 通过这些 我们希望通过这些实验来阐明 并提高我们对临床骨植入的理解 骨髓移植 我们希望我们的发现能帮助我们 修改这一重要程序，以鼓励迅速 植入而不发生移植物抗宿主病。

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.