Defining Therapeutic Potential of Clonal Stem Cell Populations using Targeted Nan

使用靶向纳米粒子确定克隆干细胞群的治疗潜力

• 批准号: 7405115
• 负责人: Dana Larocca
• 金额: $ 19.95万
• 依托单位: OCATA THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-17 至 2008-07-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7405115
• 关键词: Attention; Bacteriophages; Binding; Biological Assay; Blood Vessels; Cardiac; Cell Communication; Cell Differentiation process; Cell Lineage; Cell Separation; Cell Therapy; Cell surface; Cells; Characteristics; Dermal; Development; Disease; Enzyme-Linked Immunosorbent Assay; Epithelial; Fluorescence; Gene Expression; Genome; Germ; Goals; Heart; Human; Human Cell Line; Image; In Vitro; Individual; Injury; Label; Libraries; Life; Ligands; Methods; Molecular Profiling; Muscle Fibers; Myocardium; Peptide Phage Display Library; Peptides; Phage Display; Phase; Photography; Pluripotent Stem Cells; Population; Process; Property; Quantum Dots; Reagent; Replacement Therapy; Research; Retinal; Scientist; Screening procedure; Signal Transduction; Skin; Specificity; Stem cells; Surface; Technology; Testing; Therapeutic; Time; Tissues; base; blastomere structure; cell type; commercialization; embryonic stem cell; human embryonic stem cell; immunocytochemistry; interest; progenitor; research study; self-renewal; time use; tool

Project Summary Embryonic stem cells offer considerable potential for cell replacement therapy where cells have been lost to injury or disease because of their capacity for continual self renewal and ability to differentiate into virtually any cell type or tissue. Currently, however the process by which human embryonic stem cells (hESCs) differentiate into various mature functional cell types is poorly understood and there is a critical unmet need for methods of expanding and differentiating hESCs into desirable cell types such as epithelial, dermal, endothelial, cardiac and skeletal myocytes, etc. Scientists at Advanced Cell Technology have isolated hundreds of clonal cell populations (called lineage restricted cells, LRCs) derived from differentiating hESCs which appear to be both expandable in culture and have the properties of early progenitor cells of a multitude of mature cell types. We would like to study LRC differentiation in the context of a differentiating culture of hESCs where they receive signals from surrounding cells and matrix to better understand their therapeutic potential and how to direct their differentiation in culture. Near term, our goal is to identify specific targeting peptides for LRCs using phage display. Selection on these homogeneous progenitor populations will allow us to identify specific targeting peptides that target surface markers that might otherwise be under-represented when selecting on a hererogeneous population of differentiating hESCs. We will track the developmental fate of targeted LRCs in their native context of differentiating hESCs using quantum dot conjugated targeting peptides. These tools will allow use to study the differentiation of specific progenitor cells as it occurs in real time using time-lapse imaging. Multiplex labeling with 2 or more peptides will allow us to trace progenitor cell interactions during in vitro differentiation on hESCs. These studies will be used to select LRCs with high therapeutic potential and to develop methods for LRC differentiation. Our long term goal is to develop selected LRCs for use in regenerative therapies for skin, vasculature, and heart as well as commercialization of the LRCs and their peptide targeting agents as research reagents. . Project Narrative Embryonic stem cells offer considerable potential for cell replacement therapy where cells have been lost to injury or disease because of their capacity for continual self renewal and ability to differentiate into virtually any cell type or tissue. There is a critical unmet need for methods of expanding and differentiating hESCs in-vitro into desirable cell types such as skin, heart muscle, blood vessels, etc. We have isolated hundreds of pure lineage restricted cells (LRCs) derived from hESCs which are expandable in culture and have the properties of early progenitor cells of a multitude of mature cell types. Near term, our goal is to label specific LRCs with quantum dot labeled targeting agents so that we can track the developmental fate of LRCs in cultures of differentiating hESCs and thus determine their therapeutic potential. Our long term goal is to develop selected LRCs for use in regenerative therapies for skin, vasculature, and heart among others as well as commercialization of the LRCs and their peptide targeting agents as research reagents.

项目摘要 胚胎干细胞为细胞替代疗法提供了巨大的潜力 由于其持续自我更新的能力和分化的能力而迷失了受伤或疾病 几乎进入任何细胞类型或组织。当前，但是人类胚胎茎的过程 细胞（hESC）分化为各种成熟的功能细胞类型的理解很少，并且有一个 对将hESC扩展和区分为理想的细胞类型的临界方法的临界未满足的需求 作为上皮，皮肤，内皮，心脏和骨骼肌细胞等。高级细胞的科学家 技术已经隔离了数百个克隆细胞群（称为谱系限制细胞，LRC） 源自区分hESC，似乎在文化中可以扩展，并具有 多种成熟细胞类型的早期祖细胞的特性。我们想研究LRC 在hESC的区分文化的背景下，他们从中收到信号 周围的细胞和基质，以更好地了解其治疗潜力以及如何指导其治疗潜力 文化的分化。近期，我们的目标是使用使用LRC的特定靶向肽 噬菌体显示。对这些均质祖先种群的选择将使我们能够确定特定的 靶向靶向靶向表面标记的肽，否则 选择与hESC相差的偏差人群。我们将跟踪发展命运 使用量子点共轭的靶向LRC在其本地环境中区分hESC 靶向肽。这些工具将允许研究特定祖细胞的区分 使用延时成像实时发生。具有2个或多个肽的多重标记将使我们能够 在hESC上的体外分化过程中，痕量祖细胞相互作用。这些研究将用于 选择具有高治疗潜力的LRC，并开发LRC分化的方法。我们的漫长 术语目标是开发用于皮肤，脉管系统再生疗法的选定LRCS 以及LRC及其肽靶向剂作为研究试剂的商业化。 。项目叙述 胚胎干细胞为细胞替代疗法提供了巨大的潜力 细胞由于其连续自我的能力而因受伤或疾病而丧失 更新和分化为几乎任何细胞类型或组织的能力。有关键 对扩展和区分hESC的方法未满足的需求 细胞类型，例如皮肤，心肌，血管等。我们已经孤立了数百种 纯粹的赫斯克衍生的纯谱系限制性细胞（LRC），这些细胞在培养中可扩展 并具有多种成熟细胞类型的早期祖细胞的特性。靠近 术语，我们的目标是用标记为靶向剂的量子点标记特定的LRC，以便 我们可以在区分hESC和 因此确定其治疗潜力。我们的长期目标是开发选定的 用于皮肤，脉管系统和心脏再生疗法的LRCS 以及LRCS及其肽靶向剂作为研究的商业化 试剂。