Metabolomic Screening of Biomaterials for MSC Culture

用于 MSC 培养的生物材料的代谢组学筛选

• 批准号: 10396978
• 负责人: Johnna S Temenoff
• 金额: $ 20.67万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396978
• 关键词: Biocompatible Materials; Biological; Biological Assay; Cell Aging; Cell Count; Cell Density; Cell Surface Receptors; Cell Therapy; Cells; Cellular Metabolic Process; Chronic; Chronic Disease; Clinical Trials; DNA; Data; Development; Disease; Early identification; Gene Expression; Goals; Growth Factor; Healthcare; Heparin; Human; Hydrogels; Integrins; Laboratories; Lead; Ligands; Liquid Chromatography; Maintenance; Mass Fragmentography; Mesenchymal; Metabolic; Metabolic Pathway; Metabolism; Methodology; Mission; Mitogens; Modeling; Modulus; Musculoskeletal; N-Cadherin; Outcome Measure; PF4 Gene; Pathology; Pathway interactions; Pattern; Phenotype; Process; Property; Protocols documentation; Public Health; Regenerative Medicine; Research; Sampling; Serum; Source; Stains; Stromal Cells; Styrenes; Sulfate; Surface; Testing; Therapeutic; Tissues; United States National Institutes of Health; Work; base; beta-Galactosidase; cost; density; design; experience; fitness; immunoregulation; improved; in vivo; innovation; metabolomics; paracrine; repaired; response; screening; senescence; stem; success; tissue culture; tissue repair; tool

PROJECT SUMMARY Mesenchymal stem/stromal cells (MSCs) have transformative healthcare potential, but to achieve therapeutic cell numbers, MSCs must be culture expanded. On tissue culture poly(styrene), however, MSC expansion is constrained by replicative senescence, and cells experience progressive loss of therapeutic potency with continued expansion. The lack of large numbers of reliably potent therapeutic cells is considered one of the most critical roadblocks to the success of MSC clinical trials. However, screening of improved MSC culture conditions has been hampered by the fact that there are no characterization tools that might allow prediction of cell fitness early in culture. Metabolism is the most dynamic level of cellular response, and metabolomics may enable the identification of early signatures associated with optimal cell product quality. Therefore, it is hypothesized that early metabolomics data from MSCs cultured on biomaterials will allow prediction of cell fitness later in culture and thus promote development of materials to promote a desired cell phenotype during expansion. The objective of this application is to determine the relationship between biomaterial carrier properties, cell metabolism, and maintenance of MSC fitness during expansion. This objective will be approached through the following specific aims: 1) Evaluate the effects of altering ligand type and stiffness of the biomaterial substrate on metabolism and replicative senescence of human MSCs during expansion in serum, and 2) Evaluate the effects of the substrate heparin content and pattern of initial seeding on metabolism and replicative senescence of human MSCs during expansion in serum-free conditions. The proposed work is innovative because it uses early cellular metabolic responses to design material substrates that will promote cell expansion without senescence in a range of media compositions. Results from these studies are expected to have an important positive impact because they will lead to more efficacious expansion protocols for MSCs and thus produce more effective cell-based therapies for a wide variety of diseases.

项目摘要 间充质茎/基质细胞（MSC）具有变革性的医疗保健潜力，但要实现 治疗细胞数，MSC必须扩大培养。但是，在组织培养物聚（苯乙烯）上 MSC扩展受复制性衰老的约束，细胞经历了逐渐丧失的 持续扩展的治疗效力。缺乏大量可靠的有效治疗 细胞被认为是MSC临床试验成功的最关键的障碍之一。然而， 筛查改善的MSC培养条件的筛查已经阻碍了以下事实 表征工具可以允许培养早期预测细胞健身。代谢是最大的 细胞反应的动态水平和代谢组学可以使早期特征识别 与最佳细胞产品质量相关。因此，假设早期代谢组学数据 从生物材料培养的MSC中，将允许以后的培养物预测细胞适应性，从而促进 开发材料以促进膨胀过程中所需的细胞表型。 该应用的目的是确定生物材料载体之间的关系 在扩展过程中的特性，细胞代谢和MSC适应性的维持。这个目标将是 通过以下特定目的接近：1）评估改变配体类型的影响和 生物材料底物对人类MSC的新陈代谢和复制性衰老的刚度 血清的膨胀和2）评估底物肝素含量和初始模式的影响 在无血清膨胀期间，人类MSC的新陈代谢和复制性衰老播种 状况。 拟议的工作具有创新性，因为它使用早期的细胞代谢反应来设计材料 在一系列培养基组成中，将促进细胞扩张而无衰老的底物。结果 从这些研究中，预计将产生重要的积极影响，因为它们将导致更多 MSC的有效扩展方案，因此为宽阔的细胞疗法产生更有效的基于细胞的疗法 多种疾病。