Defining the Transcriptional Heterogeneity of Human Adipose Stromal Cells using S

使用 S 定义人类脂肪基质细胞的转录异质性

• 批准号: 7910603
• 负责人: Jason Paul Glotzbach
• 金额: $ 5.38万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7910603
• 关键词: Address; Adipose tissue; Adult; Bioinformatics; Cell Therapy; Cells; Clinical; Complex; Defect; Development; Diabetes Mellitus; Disease; Gene Expression; Genes; Goals; Heterogeneity; Histocompatibility Testing; Human; Individual; Injury; Kidney Failure; Methods; Molecular Profiling; Myocardial Infarction; Natural regeneration; Nature; Procedures; Regenerative Medicine; Research Personnel; Resolution; Source; Spinal cord injury; Stem cells; Stroke; Stromal Cells; Subgroup; Therapeutic; Tissues; base; bone; cell type; infancy; minimally invasive; novel; public health relevance; regenerative; regenerative therapy; repaired; stem cell population; tissue regeneration

DESCRIPTION (provided by applicant): Most adult tissues have minimal capacity for regeneration following injury or disease. This lack of regenerative potential presents a major clinical challenge in treating a broad range of diseases, including stroke, myocardial infarction, bone defects, spinal cord injury, diabetes, and kidney failure. To address this clinical need, a major goal of regenerative medicine is to use stem cells to repair or replace damaged or missing tissue. One of the most promising cell types for stem cell-based regenerative applications is adipose-derived stromal cells (ASCs), as they are readily isolated in large numbers from minimally invasive lipoaspiration procedures and can differentiate into several different tissue types. Many investigators have demonstrated that ASCs can differentiate into several tissue types and have proposed using these cells for tissue regeneration; this field is still in its infancy. On of the major challenges that has not been solved is the heterogeneous nature of stem cells. While stem cell populations are known to be heterogeneous, the functional consequences of this heterogeneity have not been fully elucidated. The problem of undefined heterogeneity within stem cells must be overcome before they can be used effectively for therapeutic applications. The first step to understand this heterogeneity is to elucidate the gene expression profiles of these complex cells. To address this need, we have developed a novel high resolution, high-throughput method to analyze the concurrent expression of multiple genes across multiple individual cells. The central hypothesis of this proposal is that the transcriptional heterogeneity within human adipose derived stromal cells can be defined on the single cell level, which will allow selection of cell subgroups with the greatest potential for use in cell-based therapies.

描述（由申请人提供）：大多数成人组织在受伤或疾病后具有最小的再生能力。这种再生潜力的缺乏给治疗多种疾病带来了重大的临床挑战，包括中风、心肌梗死、骨缺损、脊髓损伤、糖尿病和肾衰竭。为了满足这一临床需求，再生医学的一个主要目标是使用干细胞来修复或替换受损或缺失的组织。基于干细胞的再生应用最有前途的细胞类型之一是脂肪源性基质细胞（ASC），因为它们很容易从微创吸脂手术中大量分离出来，并且可以分化成几种不同的组织类型。许多研究人员已经证明 ASC 可以分化成多种组织类型，并提议使用这些细胞进行组织再生；这个领域仍处于起步阶段。尚未解决的主要挑战之一是干细胞的异质性。虽然已知干细胞群具有异质性，但这种异质性的功能后果尚未完全阐明。在干细胞有效用于治疗应用之前，必须克服干细胞内不确定的异质性问题。了解这种异质性的第一步是阐明这些复杂细胞的基因表达谱。为了满足这一需求，我们开发了一种新颖的高分辨率、高通量方法来分析多个单个细胞中多个基因的并发表达。该提案的中心假设是，人类脂肪来源的基质细胞内的转录异质性可以在单细胞水平上定义，这将允许选择最有潜力用于基于细胞的治疗的细胞亚群。