HiDef B8: Commercialization and scaled production of defined, robust, and cost-effective media for iPSCs

HiDef B8：用于 iPSC 的明确、稳健且经济高效的介质的商业化和规模化生产

• 批准号: 10255392
• 负责人: Paul W. Burridge
• 金额: $ 76.04万
• 依托单位: DEFINED BIOSCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-17 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10255392
• 关键词: Academia; Address; Adoption; Animals; Biological; Biological Assay; Biological Sciences; Cell Culture Techniques; Cell Differentiation process; Cell Line; Cell Maintenance; Cell Survival; Cells; Chemicals; Clinical; Culture Media; Development; Diet; Emerging Technologies; Evaluation; Fibroblast Growth Factor; Formulation; Gap Junctions; Genetic; Growth; Growth Factor; Heparin; Human; Industrialization; Industry; Industry Standard; Insulin; Laboratories; Literature; Mass Spectrum Analysis; Methodology; Mind; Modification; Molecular Sieve Chromatography; NRG1 gene; Names; Neuregulin 1; Outsourcing; Performance; Phase; Procedures; Production; Property; Proteins; Protocols documentation; Publishing; Recipe; Regulation; Research; Risk; Sampling; Schedule; Seasons; Serum Albumin; Serum-Free Culture Media; Small Business Innovation Research Grant; Sodium Chloride; Source; Stem Cell Development; Stem Cell Research; System; Technology; Testing; Therapeutic; Tissues; Transferrin; Undifferentiated; United States; Universities; Validation; Variant; Work; Xenobiotics; Yeasts; base; cell growth; cell type; clinical application; commercialization; cost; cost effective; design; expectation; experimental study; fetal bovine serum; improved; induced pluripotent stem cell; induced pluripotent stem cell technology; large scale production; member; pluripotency; stem cell technology; stem cells; success; sugar; trait

RESEARCH & RELATED Other Project Information Defined Bioscience, Inc. 7. PROJECT SUMMARY Inconsistency of growth media for cell culture is a significant problem in both industry and academia that has plagued laboratories for decades. In biopharma, cell-based and cell-derived therapies are growing at a tremendous rate and require well-defined, animal-free components to meet FDA and cGMP regulations. It is therefore not surprising that there is an increased need for and adoption of serum-free media for cell culture growth that is attributed to its superior batch-to-batch consistency and reduced risk of unwanted animal/xenobiotic contaminants. This is particularly critical to human induced pluripotent stem cells (hiPSCs), a rapidly evolving technology with wide research and clinical application. These cells present numerous advantages compared to previous technologies, including human origin, the ability to form multi-class cell systems and tissues, relative ease of production and modification, and functional relevance. Robust and well- characterized protocols are of utmost importance when culturing hiPSCs for downstream applications. High pluripotency, genetic stability, large-scale production and maintained function all must be kept in mind for hiPSCs. Yet despite the array of defined media now available for iPSCs, many of these media fail to satisfy the full needs of hiPSC research, including robustness over multiple passages and experimental needs, low cost, ease of production, weekend-free media changes and fully defined components. Such traits are critical for robust, consistent and affordable research in the hiPSC space. Just this year, our Defined Bioscience team empirically tested common defined media components over a large array of concentrations and combinations, isolating a well-defined recipe with high robustness, efficacy over >100 cell passages, and maintained success in a weekend-free passaging schedule. This media, termed B8 by the lab of scientific advisory board member Paul Burridge, met or exceeded the expectations for a Phase I SBIR development proposal. Here we will extend this work to prepare HiDef B8, a formulation of B8 finalized to optimal component concentrations and reduced cost. This optimized formulation will be tested across academic and industrial labs in the United States to confirm robustness and efficacy in streamlined and applied hiPSC culture and methodologies. We intend to make HiDef B8 an affordable, defined media for robust hiPSC culture across high passage numbers and in a weekend-free context, significantly reducing the cost and complexity of hiPSC technologies across the field. This will enable stable cell culture and a well-characterized starting point for subsequent differentiation and applied hiPSC technology efforts, while simultaneously lowering the barrier of entry for hiPSC development in the field.

研究及相关其他项目信息 定义生物科学公司 7. 项目概要 细胞培养生长培养基的不一致是工业界和学术界的一个重大问题， 几十年来一直困扰着实验室。在生物制药领域，基于细胞和细胞衍生的疗法正在快速增长 速度非常快，并且需要明确的非动物成分来满足 FDA 和 cGMP 法规的要求。这是 因此，细胞培养对无血清培养基的需求和采用不断增加也就不足为奇了 增长归因于其卓越的批次间一致性和降低的不良风险 动物/外源污染物。这对于人类诱导多能干细胞 (hiPSC) 尤为重要，hiPSC 是一种 快速发展的技术具有广泛的研究和临床应用。这些细胞呈现出许多 与以前的技术相比的优势，包括人类起源、形成多类细胞的能力 系统和组织、生产和修改的相对容易性以及功能相关性。坚固耐用- 在为下游应用培养 hiPSC 时，表征协议至关重要。高的 多能性、遗传稳定性、大规模生产和维持功能都必须牢记在心 hiPSC。然而，尽管现在有一系列可用于 iPSC 的定义培养基，但其中许多培养基未能满足 hiPSC 研究的全部需求，包括多次传代的稳健性和实验需求、低成本、 易于制作、无需周末更换介质以及完全定义的组件。这些特征对于稳健、 hiPSC 领域的一致且负担得起的研究。 就在今年，我们的定义生物科学团队对大量的常见定义培养基成分进行了实证测试。 一系列的浓度和组合，分离出一个具有高稳健性、功效超过明确定义的配方 >100 次细胞传代，并在无周末传代计划中保持成功。该媒体被称为 B8 科学顾问委员会成员 Paul Burridge 的实验室达到或超出了第一阶段 SBIR 的预期 发展建议。在这里，我们将扩展这项工作来制备 HiDef B8，这是最终达到最佳状态的 B8 配方 成分集中并降低成本。这种优化的配方将在学术界和学术界进行测试 美国的工业实验室确认简化和应用的 hiPSC 培养的稳健性和有效性 和方法论。我们打算使 HiDef B8 成为一种经济实惠的明确培养基，用于跨领域的稳健 hiPSC 培养 高传代次数且无需周末，显着降低 hiPSC 的成本和复杂性 整个领域的技术。这将使稳定的细胞培养成为可能，并为细胞培养提供一个良好表征的起点。 随后的分化和应用 hiPSC 技术的努力，同时降低了门槛 hiPSC 开发领域的入门。