Novel Bioreactor Platform for Scalable Cardiomyogenic Differentiation from Pluripotent Stem Cell-Derived Embryoid Bodies

Rungarunlert, Sasitorn; Ferreira, João N.; Dinnyés, András

doi:10.1007/7651_2016_341

Cited by 3 publications

(4 citation statements)

References 14 publications

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“…Bioreactor expansion of hPSCs on microcarriers is problematic for clinical use, as separating the microcarrier from the final cell harvest requires an additional step. On the other hand, aggregate cultivation in bioreactors may not necessarily require a detachment step for harvesting (Bartosh et al, 2010;Amit et al, 2011;Larijani et al, 2011;Dou et al, 2012;Nath et al, 2018), and clinically relevant cell numbers has been produced as aggregate in a single bioreactor (Haraguchi et al, 2015;Rungarunlert et al, 2016;Nath et al, 2017Nath et al, , 2018 (Table 3).…”

Section: Integration Of Expansion and Differentiation In Bioreactorsmentioning

confidence: 99%

“…Bioreactor culture is a unique choice for CBT production because differentiation and expansion can be done in the same vessel. Bioreactors have been used to differentiate hPSCs into different cell types, especially for cardiac (Matsuura et al, 2012;Kempf et al, 2015;Rungarunlert et al, 2016), hepatic (Vosough et al, 2013;Park et al, 2014), and neural (Yan et al, 2016) lineages. In order to provide direct methods for clinical applications, it is important to integrate expansion and differentiation, and several reports have recently been published wherein expansion and differentiation have been integrated (Lam et al, 2014;Ting et al, 2014;Fonoudi et al, 2015;Haraguchi et al, 2015).…”

Section: Integration Of Expansion and Differentiation In Bioreactorsmentioning

confidence: 99%

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Cell-Based Therapy Manufacturing in Stirred Suspension Bioreactor: Thoughts for cGMP Compliance

Nath

Harper

Rancourt

2020

Front. Bioeng. Biotechnol.

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Cell-based therapy (CBT) is attracting much attention to treat incurable diseases. In recent years, several clinical trials have been conducted using human pluripotent stem cells (hPSCs), and other potential therapeutic cells. Various private- and government-funded organizations are investing in finding permanent cures for diseases that are difficult or expensive to treat over a lifespan, such as age-related macular degeneration, Parkinson’s disease, or diabetes, etc. Clinical-grade cell manufacturing requiring current good manufacturing practices (cGMP) has therefore become an important issue to make safe and effective CBT products. Current cell production practices are adopted from conventional antibody or protein production in the pharmaceutical industry, wherein cells are used as a vector to produce the desired products. With CBT, however, the “cells are the final products” and sensitive to physico- chemical parameters and storage conditions anywhere between isolation and patient administration. In addition, the manufacturing of cellular products involves multi-stage processing, including cell isolation, genetic modification, PSC derivation, expansion, differentiation, purification, characterization, cryopreservation, etc. Posing a high risk of product contamination, these can be time- and cost- prohibitive due to maintenance of cGMP. The growing demand of CBT needs integrated manufacturing systems that can provide a more simple and cost-effective platform. Here, we discuss the current methods and limitations of CBT, based upon experience with biologics production. We review current cell manufacturing integration, automation and provide an overview of some important considerations and best cGMP practices. Finally, we propose how multi-stage cell processing can be integrated into a single bioreactor, in order to develop streamlined cGMP-compliant cell processing systems.

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Section: Integration Of Expansion and Differentiation In Bioreactorsmentioning

confidence: 99%

Section: Integration Of Expansion and Differentiation In Bioreactorsmentioning

confidence: 99%

Cell-Based Therapy Manufacturing in Stirred Suspension Bioreactor: Thoughts for cGMP Compliance

Nath

Harper

Rancourt

2020

Front. Bioeng. Biotechnol.

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“…After expansion, cells can be differentiated in the same vessel which makes bioreactor culture a unique choice for integrated biologics manufacturing. Bioreactors were used for differentiation of hPSCs into various cell types, especially for cardiac [110][111][112], hepatic [113,114], and neural [115] lineages. To provide straightforward methods for clinical applications, integration of expansion and differentiation is important and there are several reports published recently where expansion and differentiation were integrated [108,[116][117][118].…”

Section: Integrated System For Large-scale Expansion and Differentiatmentioning

confidence: 99%

Integrated Biologics Manufacturing in Stirred-Suspension Bioreactor: A Stem Cell Perspective

Nath¹,

Rancourt²

2019

Current Topics in Biochemical Engineering

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Stem cell therapy is garnering attention as several clinical trials have taken place in the recent years by using human pluripotent stem cells (hPSCs). Hundreds of biotechnological companies are investing to find a permanent cure for difficult-totreat diseases like age-related macular degeneration, Parkinson's disease, diabetes, etc. by using hPSCs. Therefore, clinical-grade cell manufacturing has become an important issue to make cell therapy products safe and effective. Current manufacturing practices are adopted from conventional antibody or protein production in the pharmaceutical industry where cells are used as a vector for producing the desired products. In cell therapy applications, cells are the products that are sensitive to physicochemical parameters and storage conditions anywhere between isolation to patient administration. Moreover, cell-based product manufacturing consists of multi-step processing, including isolation from patients, genetic modification, derivation, expansion, differentiation, purification, characterization, cryopreservation, etc. This can require long processing times and pose high risk of product contamination as well as high production cost. Herein, we discuss the current methods of biologics manufacturing and its limitations. We also review current practices for integrating and automating cell manufacturing facilities. Finally, we propose how to integrate multi-step cell processing in a single bioreactor to make the cell manufacturing practices more direct.

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“…For example, neural stem cells and neural progenitor cells are able to differentiate and develop into neurons and glia when grown in the RWV bioreactor [99,100,101]. Other examples include embryonic stem cells, pluripotent stem cells and mesenchymal stem cells, all which have been successfully propagated in RWV bioreactors and could advance RWV bioreactor-derived models [100,102,103,104,105]. The increasing utilization of RWV bioreactors for cell lines from a wide variety of tissues holds the promise of enhancing our ability to study emerging viruses that have drastic public health implications.…”

Section: Future Directions For Rwv Bioreactorsmentioning

confidence: 99%

Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

Gardner

Herbst-Kralovetz

2016

Viruses

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The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies.

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Novel Bioreactor Platform for Scalable Cardiomyogenic Differentiation from Pluripotent Stem Cell-Derived Embryoid Bodies

Cited by 3 publications

References 14 publications

Cell-Based Therapy Manufacturing in Stirred Suspension Bioreactor: Thoughts for cGMP Compliance

Cell-Based Therapy Manufacturing in Stirred Suspension Bioreactor: Thoughts for cGMP Compliance

Integrated Biologics Manufacturing in Stirred-Suspension Bioreactor: A Stem Cell Perspective

Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

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