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相当大的潜力， 因受伤或疾病而丧失，因为它们有持续自我更新的能力和分化能力 转化成几乎任何类型的细胞或组织。然而，目前人类胚胎干细胞 细胞（hESC）分化成各种成熟的功能细胞类型知之甚少， 对扩增hESC并使其分化为所需细胞类型的方法的关键未满足的需求， 如上皮细胞、真皮细胞、内皮细胞、心肌细胞和骨骼肌细胞等。 技术已经分离出数百种克隆细胞群（称为谱系限制细胞，LRC） 来源于分化中的hESC，其似乎在培养中可扩增并且具有 许多成熟细胞类型的早期祖细胞的特性。我们想学习LRC 在hESC的分化培养物的背景下，它们接收来自hESC的信号， 周围的细胞和基质，以更好地了解他们的治疗潜力，以及如何指导他们的治疗。 文化上的差异。短期内，我们的目标是确定LRC的特异性靶向肽， 噬菌体展示对这些同质祖先群体的选择将使我们能够识别特定的 靶向肽靶向表面标记物，否则当 选择分化中的hESC的异源群体。我们将追踪 使用量子点缀合的靶向LRC在其分化hESC的天然背景下的 靶向肽。这些工具将允许用于研究特定祖细胞的分化， 使用延时成像在真实的时间内发生。用2个或更多个肽进行多重标记将使我们能够 hESC体外分化过程中的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。我们漫长 长期目标是开发用于皮肤、脉管系统和心脏再生治疗的选择性LRC 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相当大的潜力， 细胞因损伤或疾病而丧失，因为它们具有持续自我调节的能力。 更新和分化成几乎任何细胞类型或组织的能力。存在一个临界 对体外扩增和分化hESC为所需细胞的方法的未满足的需求 细胞类型，如皮肤，心肌，血管等，我们已经分离出数百个 来源于hESC的纯谱系限制性细胞（LRC），在培养中可扩增 并具有多种成熟细胞类型的早期祖细胞的性质。附近 我们的目标是用量子点标记的靶向剂标记特定的LRC， 我们可以在分化的hESC培养物中追踪LRC的发育命运， 从而决定其治疗潜力。我们的长期目标是发展选定的 用于皮肤、脉管系统和心脏等的再生疗法的LRC， 以及LRC及其肽靶向剂的商业化， 试剂