Mechanisms Underlying Stem Cell Plasticity

干细胞可塑性的潜在机制

• 批准号: 7162528
• 负责人: SAUL Joseph SHARKIS
• 金额: $ 32.6万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7162528
• 关键词: Acute; Affect; Appendix; Cells; Chronic; Chronic Disease; Commit; Complement; Cystic Fibrosis; Diabetes Mellitus; Disease; Epithelial; Genes; Germ Layers; Goals; Hematopoietic; Hematopoietic stem cells; In Vitro; Incidence; Injury; Kidney Failure; Kinetics; Liver; Liver Stem Cell; Marrow; Measurement; Methods; Modeling; Natural regeneration; Phenotype; Population; Publishing; Research Design; Research Personnel; Signal Transduction; Site; Stem cells; Therapeutic; Time; Tissues; Transplantation; Wound Healing; adult stem cell; base; effusion; hematopoietic tissue; in vitro Assay; in vivo; injured; novel; progenitor; programs; release factor; repaired; response; stem cell therapy

DESCRIPTION (provided by applicant): We will establish the qualitative and quantitative potential of stem cells (SC) and committed progenitor cells of hematopoietic tissue (HSC) for the repair of damage to epithelial tissues. These studies are designed to examine the mechanisms responsible for tissue repair and regeneration. We believe in order to determine what regulates repair/regeneration we must show: a) What the factors are that induce conversion of hematopoietic stem cells into liver; b) what are the target cells responsible for the repair; c) how the cells can be delivered to the site of injury; d) how we can track the cells after transplantation; and e) what is the level of repair/regeneration over time. Our long term goals of these studies are to utilize SC from hematopoietic and non-hematopoietic tissue to offer treatment options for diseases such as Diabetes, Cystic Fibrosis, as well as liver or kidney failure. Our plan is to establish the mechanisms which allow adult SC to reprogram in response to specific injury signals. Thus our specific aims are: 1) we plan to determine the repair/regeneration potential of SC for repair of acutely or chronically injured liver. Further, we will examine the effect of injury signals on the conversion of HSC into functional cells of the injured tissue phenotype using a novel in vitro assay. Fusion is an additional mechanism which might be responsible for conversion. Therefore we will also study the consequences effusion if and when it occurs to understand this mechanism of cellular repair. Our in vitro studies will be complemented with in vivo transplant studies to determine the functional potential for SC therapy. Our aim 2) is to study which target cells can affect the repair of injured tissue. Is it possible that each tissue has its own reservoir of SC which can repair in particular circumstances? We will attempt to isolate SC from epithelial tissues by methods which we have already used to successfully isolated HSC and determine the potential for these cells to repair injured epithelial and hematopoietic tissue. Relevance: Our long term goals of these studies are to utilize SC from hematopoietic and non-hematopoietic tissue to offer treatment options for diseases such as Diabetes, Cystic Fibrosis, as well as liver or kidney failure. Our plan is to establish the mechanisms which allow adult SC to reprogram in response to specific injury signals.

描述（由申请人提供）：我们将建立造血组织（SC）和造血组织（HSC）的祖细胞的定性和定量潜力，以修复上皮组织的损害。这些研究旨在检查负责组织修复和再生的机制。我们认为，为了确定哪种调节修复/再生，我们必须显示：a）诱导造血干细胞转化为肝脏的因素； b）负责修复的目标细胞是什么； c）如何将细胞输送到损伤部位； d）移植后如何跟踪细胞； e）随着时间的推移，维修/再生的水平是多少。这些研究的长期目标是利用造血性和非山摩托教育组织的SC为糖尿病，囊性纤维化以及肝脏或肾脏衰竭等疾病提供治疗选择。我们的计划是建立允许成人SC以响应特定伤害信号进行重新编程的机制。因此，我们的具体目的是：1）我们计划确定SC修复急性或长期损伤肝脏的修复/再生潜力。此外，我们将使用一种新型的体外测定法检查损伤信号对HSC转化为受伤组织表型的功能细胞的影响。融合是一种可能导致转化的附加机制。因此，如果以及发生这种情况以了解这种细胞修复机制，我们还将研究后果积液。我们的体外研究将补充体内移植研究，以确定SC治疗的功能潜力。我们的目标2）是研究哪些靶细胞会影响受伤组织的修复。每个组织都有可能在特定情况下可以修复的SC储层吗？我们将尝试通过已经成功地分离出HSC的方法将SC从上皮组织中分离出来，并确定这些细胞修复受伤的上皮和造血组织的潜力。相关性：这些研究的长期目标是利用造血和非造血组织组织的SC来为糖尿病，囊性纤维化以及肝脏或肾衰竭等疾病提供治疗选择。我们的计划是建立允许成人SC以响应特定伤害信号进行重新编程的机制。