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

• 批准号: 10468688
• 负责人: DARNELL KAIGLER
• 金额: $ 43.47万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10468688
• 关键词: Address; Adherence; Adult; Affect; Age; Angiogenic Factor; Automobile Driving; Biological; Biological Process; Bone Marrow; Bone Regeneration; Bone Tissue; Cell Culture Techniques; Cell Separation; Cell Therapy; Cells; Chronic; Clinical; Clinical Trials; Computer Models; Data; Dental; Dental Pulp; Development; Disease; ENG gene; Emerging Technologies; Fatty acid glycerol esters; Funding Mechanisms; Gene Expression; Gene Expression Profile; Genetic Transcription; Gingiva; Health; Immunophenotyping; Inflammation; Inflammatory; Knowledge; Link; Maintenance; Mesenchymal Stem Cells; Methods; Molecular; Molecular Biology; Molecular Profiling; Muscle; Natural regeneration; Operative Surgical Procedures; Oral; Osteogenesis; Outcome; Pathway interactions; Performance; Phenotype; Physiological; Population; Population Heterogeneity; Production; Property; Regenerative Medicine; Regulation; Reporting; Research; Rodent Model; Role; Signal Pathway; Sorting - Cell Movement; Specificity; Technology; Testing; Therapeutic; Time; Tissues; Tooth structure; United States National Institutes of Health; Work; adult stem cell; alveolar bone; angiogenesis; base; bone; clinical translation; healthy volunteer; in vivo; innovation; insight; interest; machine learning algorithm; molecular phenotype; next generation sequencing; novel; oral tissue; osteogenic; population based; regeneration model; regenerative; regenerative cell; regenerative therapy; screening; stem cell differentiation; stem cell population; stem cell self renewal; stem cell therapy; stem cells; stemness; transcription factor; transcriptome

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.

摘要 间充质干细胞(MSCs)在再生医学细胞治疗和治疗中具有广泛的潜力 可以从各种不同的组织中分离出来。尽管来自不同组织的MSCs具有表型 同样，它们临床应用的障碍是它们的营养和再生特性的高度可变性。这 可变性表明，指导MSC特性的分子机制存在固有的差异 然而，到目前为止，这些差异在不同的MSC群体之间还没有明确的定义。为此，我们有 初步证据表明，MSC表型与其再生结果相关。在本研究中，我们的目标是 为了阐明不同MSC群体的分子和细胞特性如何决定他们的 再生特性。我们的假设是来自不同组织的MSCs具有不同的再生能力 与由基因表达和转录所定义的特定分子图谱相关的特性 活动。为了验证这一假设，提出的项目有三个具体目标(SA)。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 不同的骨髓间充质干细胞。SA2将决定细胞和分子特性的差异如何 MSCs与MSC表型相关。最后，在SA3中，我们将确定分子轮廓和 MSCs的细胞活动决定了它们的再生特性。拟议研究的结果将 提供关于MSCs的不同分子特征如何决定其生物学和 生理特性。在治疗方面，这将使创新的发展成为可能 MSC疗法的筛选技术，以确定和丰富最适合的MSC 具体的治疗应用。