Bioreactors for cell therapies: Current status and future advances

Eaker, Shannon; Abraham, Eytan; Allickson, Julie; Brieva, Thomas A.; Baksh, Dolores; Heathman, Thomas R.J.; Mistry, Biren; Zhang, Nan

doi:10.1016/j.jcyt.2016.09.011

Cited by 44 publications

(36 citation statements)

References 26 publications

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“…Research on iPSCs paved the way to identify the molecular mechanisms underlying pluripotency of all kinds of chicken stem cells (Lu et al 2011) as well as providing a better tool for vaccine manufacturing (Shittu et al 2016). Although feeder cell, serum and growth factor employment in culture conditions leads to the successful derivation and culture of chicken stem cells, it presents a risk of propagating contaminating virus particles making these supplements unsuitable for vaccine manufacturing and cell-based transgenic technology (Halme and Kessler 2006;Eaker et al 2017;Gupta et al 2017).…”

Section: Derivation Of Chicken Stem Cellsmentioning

confidence: 99%

The evolution of chicken stem cell culture methods

Farzaneh

Attari

Mozdziak

et al. 2017

British Poultry Science

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1. The avian embryo is an excellent model for studying embryology and the production of pharmaceutical proteins in transgenic chickens. Furthermore, chicken stem cells have the potential for proliferation and differentiation and emerged as an attractive tool for various cell-based technologies. 2. The objective of these studies is the derivation and culture of these stem cells is the production of transgenic birds for recombinant biomaterials and vaccine manufacture, drug and cytotoxicity testing, as well as to gain insight into basic science, including cell tracking. 3. Despite similarities among the established chicken stem cell lines, fundamental differences have been reported between their culture conditions and applications. Recent conventional protocols used for expansion and culture of chicken stem cells mostly depend on feeder cells, serum-containing media and static culture. 4. Utilising chicken stem cells for generation of cell-based transgenic birds and a variety of vaccines requires large-scale cell production. However, scaling up the conventional adherent chicken stem cells is challenging and labour intensive. Development of a suspension cell culture process for chicken embryonic stem cells (cESCs), chicken primordial germ cells (PGCs) and chicken induced pluripotent stem cells (ciPSCs) will be an important advance for increasing the growth kinetics of these cells. 6. This review describes various approaches and suggestions to achieve optimal cell growth for defined chicken stem cells cultures and use in future manufacturing applications.

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Section: Derivation Of Chicken Stem Cellsmentioning

confidence: 99%

The evolution of chicken stem cell culture methods

Farzaneh

Attari

Mozdziak

et al. 2017

British Poultry Science

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“…Several cell products have faced failure owing to challenges in designing robust, scalable, cost‐effective manufacturing processes (Brandenberger et al, 2011; Kirouac & Zandstra, 2008; Rowley, Abraham, Campbell, Brandwein, & Oh, 2012). Tools such as stirred suspension bioreactors are a valuable platform for cost‐effective and reproducible production of high‐quality cell therapies (Eaker et al, 2017). Shifting from static to bioreactor suspension culture is a critical decision for cell therapy manufacturing during the product development cycle.…”

Section: Discussionmentioning

confidence: 99%

Large‐scale expansion of feeder‐free mouse embryonic stem cells serially passaged in stirred suspension bioreactors at low inoculation densities directly from cryopreservation

Borys

Roberts

et al. 2020

Biotech & Bioengineering

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Embryonic stem cells (ESCs) have almost unlimited proliferation capacity in vitro and can retain the ability to contribute to all cell lineages, making them an ideal platform material for cell‐based therapies. ESCs are traditionally cultured in static flasks on a feeder layer of murine embryonic fibroblast cells. Although sufficient to generate cells for research purposes, this approach is impractical to achieve large quantities for clinical applications. In this study, we have developed protocols that address a variety of challenges that currently bottleneck clinical translation of ESCs expanded in stirred suspension bioreactors. We demonstrated that mouse ESCs (mESCs) cryopreserved in the absence of feeder cells could be thawed directly into stirred suspension bioreactors at extremely low inoculation densities (100 cells/ml). These cells sustained proliferative capacity through multiple passages and various reactor sizes and geometries, producing clinically relevant numbers (109 cells) and maintaining pluripotency phenotypic and functional properties. Passages were completed in stirred suspension bioreactors of increasing scale, under defined batch conditions which greatly improved resource efficiency. Output mESCs were analyzed for pluripotency marker expression (SSEA‐1, SOX‐2, and Nanog) through flow cytometry, and spontaneous differentiation and teratoma analysis was used to demonstrate functional maintenance of pluripotency.

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“…Considerations for current and future advances in bioreactors for cell therapies has been reviewed. 8,9 Moreover, considering COGs for producing a cell therapy product has also been reviewed. 10 The manufacturing cost is a key consideration in advancing regenerative medicine therapies to the clinic and widespread commercialization.…”

Section: Cell Manufacturing and Scale-up/outmentioning

confidence: 99%

Improving patient outcomes with regenerative medicine: How the Regenerative Medicine Manufacturing Society plans to move the needle forward in cell manufacturing, standards, 3D bioprinting, artificial intelligence-enabled automation, education, and training

Hunsberger¹,

Simon

Zylberberg

et al. 2020

Stem Cells Translational Medicine

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The Regenerative Medicine Manufacturing Society (RMMS) is the first and only professional society dedicated toward advancing manufacturing solutions for the field of regenerative medicine. RMMS's vision is to provide greater patient access to regenerative medicine therapies through innovative manufacturing solutions. Our mission is to identify unmet needs and gaps in regenerative medicine manufacturing and catalyze the generation of new ideas and solutions by working with private and public stakeholders. We aim to accomplish our mission through outreach and education programs and securing grants for public-private collaborations in regenerative medicine manufacturing. This perspective will cover four impact areas that the society's leadership team has identified as critical: (a) cell manufacturing and scale-up/out, respectively, for allogeneic and autologous cell therapies, (b) standards for regenerative medicine, (c) 3D bioprinting, and (d) artificial intelligence-enabled automation. In addition to covering these areas and ways in which the society intends to advance the field in a collaborative nature, we will also discuss education and training. Education and training is an area that is critical for communicating the current challenges, developing solutions to accelerate the commercialization of the latest technological advances, and growing the workforce in the rapidly expanding sector of regenerative medicine. K E Y W O R D S stem cells, technology, tissue engineering, tissue regenerationThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Bioreactors for cell therapies: Current status and future advances

Cited by 44 publications

References 26 publications

The evolution of chicken stem cell culture methods

The evolution of chicken stem cell culture methods

Large‐scale expansion of feeder‐free mouse embryonic stem cells serially passaged in stirred suspension bioreactors at low inoculation densities directly from cryopreservation

Improving patient outcomes with regenerative medicine: How the Regenerative Medicine Manufacturing Society plans to move the needle forward in cell manufacturing, standards, 3D bioprinting, artificial intelligence-enabled automation, education, and training

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