التفاصيل البيبلوغرافية
| العنوان: |
Intensifying the manufacture of hiPSC therapy products through metabolic and process understanding |
| المؤلفون: |
Serra, Margarida, Vicente, Pedro, Gomes, Catarina, Almeida, Joana, AM Pais, Daniel, Abecasis, Bernardo, Paiva, Marta, Isidro, Inês A, Alves, Paula M, Mertinez-Turrillas, Rebeca, Rodriguez-Madoz, Juan R., Aspegren, Anders, Domian, Ibrahim |
| المصدر: |
Integrated Continuous Biomanufacturing IV |
| بيانات النشر: |
ECI Digital Archives |
| سنة النشر: |
2019 |
| المجموعة: |
Engineering Conferences International: ECI Digital Archives |
| مصطلحات موضوعية: |
cell therapy, hiPSC-derived cardiomyocytes, hiPSC-derived hepatocytes, three-dimensional culture, perfusion, omics technologies, Engineering |
| الوصف: |
In vitro differentiation of human induced pluripotent stem cells into specific lineages such as cardiomyocytes (hPSC-CM) and hepatocytes (hPCS-Hep) is a crucial process to enable their application in cell therapy and drug discovery. Nevertheless, despite the remarkable efforts over the last decade towards the implementation of protocols for hPSC expansion and differentiation, there are some technological challenges remaining include the low scalability and differentiation yields. Additionally, generated cells are still immature, closely reminiscent of fetal/embryonic cells in what regards phenotype and function. In this study, we aim to overcome this hurdle by devising bioinspired and integrated strategies to improve the generation and functionality of these hiPSC-derivatives. We also applied robust multi-parametric techniques including proteomics, transcriptomics, metabolomics and fluxomics as complementary analytical tools to support bioprocess optimization and product characterization. We cultured hiPSC as 3D aggregates in stirred-tank bioreactors (STB) operated in perfusion and used a capacitance probe for in situ monitoring of cell growth/differentiation. After cell expansion, the hepatic differentiation step was integrated by addition of key soluble factors and controlling the dissolved oxygen concentration at various stages of the process to generate populations enriched for definitive endoderm, hepatocyte progenitors and mature hepatocytes. The analyses of hepatic markers expression throughout the stages of the differentiation confirmed that hepatocyte differentiation was improved in 3D spheroids when compared to 2D culture. Noteworthy, these hiPSC-HLC exhibited functional characteristics typical of hepatocytes (albumin production, glycogen storage and CYP450 activity). We also demonstrate the potential of dielectric spectroscopy to monitor cell expansion and hepatic differentiation in STB. For CM differentiation, we relied on the aggregation of hPSC-derived cardiac progenitors to establish a scalable ... |
| نوع الوثيقة: |
text |
| اللغة: |
unknown |
| العلاقة: |
https://dc.engconfintl.org/biomanufact_iv/44Test |
| الإتاحة: |
https://dc.engconfintl.org/biomanufact_iv/44Test |
| رقم الانضمام: |
edsbas.82AFF9C2 |
| قاعدة البيانات: |
BASE |
