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.

用于制造COVID-19 iPSC衍生细胞的符合CGMP的封闭细胞培养系统