Redefining mesenchymal stem cells: using their cellular and molecular phenotypes to determine their regenerative and therapeutic properties

重新定义间充质干细胞：利用其细胞和分子表型来确定其再生和治疗特性

基本信息

批准号：
10687814
负责人：
DARNELL KAIGLER
金额：
$ 40.55万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-08-31
项目状态：
已结题

项目摘要

ABSTRACT Mesenchymal stem cells (MSCs) have broad-based potential in regenerative medicine cell therapies and can be isolated from a variety of different tissues. Though MSCs from different tissues are phenotypically similar, a barrier to their clinical use is the high variability of their trophic and regenerative properties. This variability suggests that inherent differences exist in the molecular machinery guiding MSC properties between different MSC populations, yet, to date, these differences are ill-defined. To this end, we have preliminary evidence that MSC phenotypes correlate to their regenerative outcomes. In this study, we aim to elucidate how the molecular and cellular properties of distinct MSC populations determine their regenerative properties. Our hypothesis is that MSCs from different tissues have different regenerative properties which correlate to specific molecular profiles defined by gene expression and transcriptional activity. To test this hypothesis, the project proposed has three Specific Aims (SAs). In SA1, we will determine how tissue-specificity dictates gene expression and dynamic transcription factor activity of distinct MSCs. SA2 will determine how differences in the cellular and molecular properties of MSCs correlate to MSC phenotype. Finally, in SA3, we will determine how the molecular profiles and cellular activities of MSCs dictate their regenerative properties. Findings of the proposed study will provide novel insights about how the distinct molecular profiles of MSCs dictate their biological and physiological properties. In a therapeutic context, this would enable the development of innovative screening technologies for MSC therapies to identify and enrich for the most appropriate MSC for the specific therapeutic application.

抽象的间充质干细胞（MSC）在再生医学细胞疗法中具有广泛的基础潜力，可以从各种不同的组织中分离出来。尽管来自不同组织的MSC是表型类似的临床用途障碍是其营养和再生特性的高度差异。这可变性表明分子机械指导MSC属性中存在固有差异迄今为止，在不同的MSC人群之间，这些差异是错误的。为此，我们有 MSC表型与其再生结果相关的初步证据。在这项研究中，我们的目标为了阐明不同MSC种群的分子和细胞特性如何确定其再生特性。我们的假设是来自不同组织的MSC具有不同的再生与特定的分子谱相关的特性，这些特征由基因表达和转录定义活动。为了检验这一假设，该项目提出了三个特定目标（SAS）。在SA1中，我们将确定组织特异性如何决定基因表达和动态转录因子活性不同的MSC。 SA2将确定细胞和分子特性的差异 MSC与MSC表型相关。最后，在SA3中，我们将确定分子曲线和 MSC的细胞活性决定其再生特性。拟议研究的发现将提供有关MSC的独特分子谱的新见解生理特性。在治疗背景下，这将使创新的发展筛查技术用于MSC疗法，以识别和丰富最合适的MSC 具体的治疗应用。