A MURINE MODEL OF HEMATOPOIETIC ENGRAFTING CELLS

小鼠造血移植细胞模型

基本信息

批准号：
6913594
负责人：
IAN K MCNIECE
金额：
$ 40.88万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-07-01 至 2007-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6913594
关键词：
apoptosis biological models cell population study cell type cellular immunity cytokine growth factor growth media hematopoietic tissue transplantation immune tolerance /unresponsiveness laboratory mouse neutrophil platelets polymerase chain reaction stem cell transplantation tissue /cell culture transplantation immunology

项目摘要

DESCRIPTION (provided by applicant): High dose chemotherapy followed by stem cell transplantation (SCT) is routinely used for treatment of patients with hematological malignancies and solid tumors. Patients receiving SCT have significant periods of neutropenia and thrombocytopenia and prolonged periods of depressed immune cells, particularly recipients of cord blood (CB) grafts. Ex vivo expansion of hematopoietic grafts could provide more rapid engraftment and decrease graft failure of CB recipients. Despite extensive studies to determine the hematopoietic cells that are responsible for rapid hematopoietic recovery, there is debate to which cells provide recovery of neutrophils, platelets and immune cells. Therefore there is debate as to which cells should be expanded ex vivo. We hypothesize that i) distinct mature precursor cells are responsible for neutrophil, platelet and lymphoid engraftment, ii) intermediate engraftment is provided by committed and/or multipotential precursors, and iii) long term engraftment is provided by totipotent hematopoietic stem cells (HSC). Using a mouse transplant model we will determine the cells providing short term engraftment, intermediate cell engraftment and long term durable engraftment These studies will evaluate the contribution of candidate stem cell populations to both short term and long term engraftment The goal of this project is to identify and characterize the murine cells responsible for recovery of each lineage of hematopoietic cells. In addition, mouse ex vivo expansion studies will be conducted to characterize the growth factor cocktails that stimulate optimal generation of each of these populations. We also hypothesize that ex vivo expanded cells require additional growth factors when infused in vivo and we will determine the growth factors that provide optimal engraftment of expanded cells in vivo. These studies will be combined to identify the optimal numbers of each population and optimal timing of transplantation and growth factor treatment We propose that these studies will lead to better defined mouse grafts that provide optimal engraftment and will then provide the basis for evaluating human hematopoietic grafts for equivalent populations and further ex vivo expansion studies.

描述（由申请人提供）：高剂量化疗，然后是干细胞移植（SCT）通常用于治疗血液恶性肿瘤和实体瘤患者。接受SCT的患者患有大量的中性粒细胞减少症和血小板减少症，并且免疫细胞抑郁症的长期，特别是脐带血（CB）移植物的受体。造血移植物的体内扩展可以提供更快的植入，并减少CB受体的移植失败。尽管进行了广泛的研究，以确定负责快速造血恢复的造血细胞，但仍有争议细胞提供中性粒细胞，血小板和免疫细胞的恢复。因此，关于哪些细胞应在体内扩展存在争议。我们假设i）i）不同的成熟前体细胞负责中性粒细胞，血小板和淋巴机的植入，ii）中间植入由致力于和/或多能性前体提供，以及III）长期植入由全部功能性血肿干细胞（HSC）提供。使用小鼠移植模型，我们将确定提供短期植入，中间细胞植入和长期耐用植入的细胞，这些研究将评估候选干细胞群体对短期和长期植入的候选干细胞群体的贡献。该项目的目标是识别和表征负责鼠细胞恢复血肿细胞的鼠细胞。此外，将进行小鼠外体扩张研究，以表征刺激这些人群最佳产生的生长因子鸡尾酒。我们还假设，当体内注入体内时，体内扩展的细胞需要其他生长因子，我们将确定可提供体内扩张细胞的最佳植入的生长因子。这些研究将结合起来，以确定每个人群的最佳数量以及移植和生长因子治疗的最佳时机，我们建议这些研究将导致更好定义的小鼠移植物，从而提供最佳的植入，然后为评估人类造血植物移植物提供基础，以评估人类的同等种群，并进一步扩张研究。