CGMP Compliant Closed Cell Culture System for culturing iPSC derived lung epithelial cells to COVID19 Therapy

符合 CGMP 的封闭细胞培养系统，用于培养 iPSC 衍生的肺上皮细胞以进行 COVID19 治疗

• 批准号: 10343488
• 负责人: John Collins
• 金额: $ 15.55万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10343488
• 关键词: Address; Affect; Air; Algorithms; Alleles; Alveolar; Alveolar Cell; Automation; Award; Biological; Biomanufacturing; Biotechnology; Bronchopulmonary Dysplasia; COVID-19; COVID-19 mortality; COVID-19 treatment; CXCR4 gene; Carbon Dioxide; Cell Culture System; Cell Culture Techniques; Cell Maintenance; Cell Therapy; Cells; Cessation of life; Clinical Research; Clinical Trials; Combined Modality Therapy; Complex; Cryopreservation; Cyclic GMP; Derivation procedure; Development; Disease; Endoderm; Endothelial Cells; Environment; Epithelial; Epithelial Cells; Equilibrium; Exhibits; Fluorochrome; Functional disorder; Generations; Growth; Healthcare Industry; Human; Immune system; Infection; Inhalation; Kinetics; Lead; Legal patent; Liquid substance; Logistics; Lung; Mesenchymal Stem Cells; Methods; Microbe; Modern 1601-history; Monitor; Natural Killer Cells; Natural regeneration; Parents; Patients; Phase; Physiologic pulse; Population; Process; Proliferating; Protocols documentation; Pulmonary Fibrosis; Pump; Reagent; Reporter; Reporting; Reproducibility; Research; Risk; Scheme; Source; Stress; Structure; Structure of parenchyma of lung; System; T-Lymphocyte; Technology; Temperature; Therapeutic; Time; Tissue Sample; Tissues; Transition Temperature; Transportation; Up-Regulation; Validation; Vial device; Virus; activin A; alveolar epithelium; animal safety; base; combat; cost; differentiation protocol; epithelial stem cell; exosome; expectation; flasks; gene therapy; genome integrity; improved; induced pluripotent stem cell; lung repair; manufacturing facility; manufacturing scale-up; meetings; meter; novel; novel coronavirus; operation; pandemic disease; point of care; pressure; pressure sensor; prevent; progenitor; regeneration potential; repaired; response; safety study; scale up; sensor; stem cells; stressor; success; transcriptomics

CGMP Compliant Closed Cell Culture System for Manufacturing iPSC Derived Cells for COVID-19 Clinical Trials Abstract The novel Coronavirus represents one of the largest pandemics in modern history, reaching around 100 million cases and two million deaths reported worldwide. Alveolar cells, endothelial cells, and lung structure are severely damaged during the infection stage. Insufficient alveolar repair may increase lung vulnerability to inhaled microbes and substances or lead to lung fibrosis. So globally, the healthcare industry uses several methods to suppress the threat caused by the virus, including the use of living therapies such as natural killer cells, T-cells, stem cells combination therapies, and exosomes. Currently, mesenchymal stem cells are already showing intriguing potential for the treatment of COVID-19 but have not been found to have detectable potential to regenerate lung epithelium. Though generation of complex alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli from induced pluripotent stem cells (iPSCs) have been challenging, recently, using iPSCs and directed differentiation, lung epithelial progenitor cells and AEC2s were generated for potential regenerative gene or cell therapies. The advancement of these iPSC- based personalized cell therapies, capable of effectively repairing lung epithelium, is currently hindered by biomanufacturing challenges. 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 further advance of iPSC-based personalized COVID-19 therapy is currently limited by the difficulty to generate and differentiate iPSCs for large populations at an affordable cost. Therefore Biopico Systems Inc will solve such challenges by developing an automated cGMP Compliant Closed Cell Culture System for manufacturing iPSC derived cells based clinical trials for regenerating lung epithelium damaged by COVID-19. To commercialize Biopico's scaled up “CellsMX” system, optimization of closed media exchange system with modified pumping algorithm and validation of GMP manufacturing protocols will be performed in this research. Further, even if a large number of patients need iPSC-based personalized cell therapies, the system can be deployed at the point of care avoiding risks associated with transportation, logistics, tracking, and recording. Biopico will submit regulatory documents with FDA for the CellsMX system that will be released to the customers for their pre-IND applications.

符合 CGMP 的封闭细胞培养系统，用于制造 COVID-19 的 iPSC 衍生细胞 临床试验 抽象的 新型冠状病毒是现代历史上最严重的流行病之一，影响人数达到约 100 人 全球报告了 100 万例病例和 200 万人死亡。肺泡细胞、内皮细胞和肺结构 在感染阶段受到严重损害。肺泡修复不充分可能会增加肺部的脆弱性 吸入微生物和物质或导致肺纤维化。因此，在全球范围内，医疗保健行业使用多种 抑制病毒造成的威胁的方法，包括使用自然疗法等活疗法 杀伤细胞、T 细胞、干细胞联合疗法和外泌体。目前，间充质干细胞 已经显示出治疗 COVID-19 的令人着迷的潜力，但尚未被发现 可检测到的肺上皮再生潜力。虽然复杂肺泡上皮2型的产生 细胞（AEC2），来自诱导多能干细胞（iPSC）的肺泡的兼性祖细胞 最近，使用 iPSC 和定向分化、肺上皮祖细胞和 AEC2 是为潜在的再生基因或细胞疗法而生成的。这些 iPSC 的进步- 能够有效修复肺上皮的个性化细胞疗法目前受到阻碍 生物制造的挑战。尽管有一些方法已经使衍生、增长和分化 iPSC 的效率更高，但重编程功效、基因组完整性、 以及源自患者组织样本的 iPSC 的发育潜力。这些变化包括批次 依赖或技术人员依赖的分化效率、细菌或真菌污染风险、CO2 或 电池维护期间的 O2 浓度水平压力、高成本或交叉污染风险 集中式生物制造设施，以及 cGMP 标准或法规遵从性的要求。进一步的 基于 iPSC 的个性化 COVID-19 疗法的进展目前因难以生成和使用而受到限制 以可承受的成本为大量人群提供差异化​​ iPSC。因此 Biopico Systems Inc 将解决这样的问题 开发符合 cGMP 标准的自动化闭式细胞培养系统来应对挑战 基于 iPSC 衍生细胞的临床试验，用于再生受 COVID-19 损伤的肺上皮。到 将 Biopico 的放大“CellsMX”系统商业化，优化封闭式媒体交换系统 修改后的泵送算法和 GMP 生产协议的验证将在此进行 研究。此外，即使大量患者需要基于 iPSC 的个性化细胞疗法， 系统可以部署在护理点，避免与运输、物流、跟踪、 和录音。 Biopico 将向 FDA 提交 CellsMX 系统的监管文件，该系统将 向客户发布其预 IND 申请。