CGMP Compliant Closed Cell Culture System for Reproducible De-differentiation of human somatic cells into iPSCs

符合 CGMP 的封闭细胞培养系统，可将人类体细胞可重复地去分化为 iPSC

• 批准号: 10239244
• 负责人: John Collins
• 金额: $ 61.76万
• 依托单位: BIOPICO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10239244
• 关键词: Address; Air; Algorithms; Alleles; Antibodies; Automation; Biological; Biomanufacturing; Biotechnology; Carbon Dioxide; Cell Culture System; Cell Culture Techniques; Cell Maintenance; Cell Therapy; Cells; Cellular Morphology; Characteristics; Custom; Cyclic GMP; Derivation procedure; Development; Differentiation and Growth; Disease; Environment; Equilibrium; Feasibility Studies; Fibroblasts; Film; Formulation; Freezing; Gene Expression; Goals; Growth; Guidelines; Human; Image; Immunologics; In Vitro; Individual; Legal patent; Licensing; Liquid substance; Logistics; Malignant Neoplasms; Manuals; Messenger RNA; Microscope; Monitor; Motor; Organ; Patients; Performance; Periodicity; Phase; Population; Process; Production; Protocols documentation; Pump; Reagent; Reproducibility; Research; Research Personnel; Risk; Sampling; Somatic Cell; Source; Stains; Stimulus; Stress; Syringes; System; Systems Integration; Technology; Temperature; Testing; Therapeutic; Therapeutic Uses; Time; Tissue Sample; Tissue Therapy; Tissues; Transfection; Transplantation; Transportation; Vial device; Waiting Lists; base; cost; deep learning algorithm; design; dosage; expectation; flasks; genome integrity; improved; induced pluripotent stem cell; meter; novel; operation; personalized medicine; point of care; pressure; pressure sensor; quality assurance; stem cell therapy; stem cells; stressor; success; wasting

CGMP Compliant Closed Cell Culture System for Reproducible De-differentiation of human somatic cells into iPSCs Abstract The advancement of iPSC-based personalized cell therapies is currently hindered by the challenges in the biomanufacturing of therapeutic cells. Despite approaches that have made the derivation, growth and differentiation of iPSCs more efficient, there remains significant variability in reprogramming efficacy, genomic integrity and developmental potential of iPSCs derived from patient tissue samples. These variabilities include lot-dependent or technician-dependent differentiation efficiency, bacterial or fungal contamination risks, CO2 or O2 concentration level stresses during cell maintenance, high costs or cross- contamination risks with centralized biomanufacturing facility and requirement of cGMP criteria or regulatory compliance. The difference of iPSCs derived from the same sample in their in-vitro growth characteristics and their inability to re-differentiate into the desired tissue type will cause serious problems in therapy. The further advance of iPSC-based personalized medicine is currently limited by the difficulty to generate iPSCs for large populations and at an affordable cost. Therefore Biopico Systems Inc will solve such challenges by developing an automated cGMP Compliant Closed Cell Culture System for reproducible de-differentiation of human somatic cells into iPSCs. To commercialize Biopico's “CellsMX” system, optimization of closed media exchange system and integration of customized mRNA/ media formulation front-end for reprogramming will be performed in this Phase II research. The CellsMX system will provide quality assurance to the customers for mass production under cGMP guidelines, as operating license are issued to biological entities along with how cells are produced, tested, and released for therapeutic use. Further, even, if a large number of patients need iPSC-based personalized cell therapies, under CellsMX closed system, patient cells are not cross-contaminated and the system can be deployed at the point of care avoiding high costs and risks associated with the transportation, logistics, tracking, and recording. While patient-specific iPSC strategy's reduction of immunologic stimulus will drive the initial market segment for the CellsMX system, Biopico will develop a suite of products for several of such therapeutic culture processes.

CGMP符合人类可再现脱不同的闭合细胞培养系统 体细胞进入IPSC 抽象的 目前，基于IPSC的个性化细胞疗法的进步受到了挑战 治疗细胞的生物制造。尽管方法已经导致了推导，增长和 IPSC的差异更有效，重编程效率的差异很大， 源自患者组织样本的IPSC的基因组完整性和发育潜力。这些 变异性包括依赖性或技术人员依赖的分化效率，细菌或真菌 污染风险，二氧化碳或O2浓度水平应力在维持细胞，高成本或交叉期间 具有集中生物制造设施的污染风险以及CGMP标准或监管的要求 遵守。 IPSC在其体外生长特征中得出的IPSC差异 他们无法重新分化为所需的组织类型将导致严重的治疗问题。 目前，基于IPSC的个性化医学的进一步进步受到了难以生成IPSC的限制 对于大量人口，以负担得起的成本。因此，传播系统公司将解决此类挑战 开发自动化CGMP符合CGMP的闭孔培养系统，用于可再现的脱不同 人类体细胞进入IPSC。为了商业化传播的“细胞MX”系统，优化了封闭的 媒体交换系统和定制mRNA/媒体公式前端的集成 重新编程将在此II阶段研究中进行。细胞MX系统将提供质量 根据CGMP指南向客户保证大规模生产，因为颁发了运营许可证 生物实体以及如何生产，测试和释放细胞以供治疗。此外，甚至 如果大量患者需要基于IPSC的个性化细胞疗法，则在细胞MX封闭系统下， 患者细胞没有交叉污染，可以在护理点部署系统以避免高 与运输，物流，跟踪和记录相关的成本和风险。而患者特定于患者 IPSC策略减少免疫刺激将推动细胞MX的初始市场细分 系统，传播将为几种此类治疗培养过程开发一套产品。