Single-Use Bioreactors for Human Pluripotent and Adult Stem Cells: Towards Regenerative Medicine Applications

Rodrigues, Carlos Alberto Chirano

doi:10.3390/bioengineering8050068

Cited by 18 publications

(6 citation statements)

References 129 publications

(135 reference statements)

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“…The main advantages of disposable bioreactors include savings on utilities, labor and time related to cleaning and sterilization and significantly reduced contamination concerns due to pre-sterilized equipment and process monitoring sensors [ 164 , 165 ]. Furthermore, preparation time between batches is significantly shortened by applying single-use technologies instead of CIP (cleaning-in-place) and SIP (sterilization-in-place) procedures, making the process pipeline faster and more efficient and resulting in increased overall plant productivity [ 166 ]. Disposable parts of STR usually include system parts in direct contact with cultivated cells, such as vessel, probes and impellers.…”

Section: General Aspects Of Bioreactors For Proliferation and Differe...mentioning

confidence: 99%

Bioengineering Outlook on Cultivated Meat Production

et al. 2022

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Cultured meat (also referred to as cultivated meat or cell-based meat)—CM—is fabricated through the process of cellular agriculture (CA), which entails application of bioengineering, i.e., tissue engineering (TE) principles to the production of food. The main TE principles include usage of cells, grown in a controlled environment provided by bioreactors and cultivation media supplemented with growth factors and other needed nutrients and signaling molecules, and seeded onto the immobilization elements—microcarriers and scaffolds that provide the adhesion surfaces necessary for anchor-dependent cells and offer 3D organization for multiple cell types. Theoretically, many solutions from regenerative medicine and biomedical engineering can be applied in CM-TE, i.e., CA. However, in practice, there are a number of specificities regarding fabrication of a CM product that needs to fulfill not only the majority of functional criteria of muscle and fat TE, but also has to possess the sensory and nutritional qualities of a traditional food component, i.e., the meat it aims to replace. This is the reason that bioengineering aimed at CM production needs to be regarded as a specific scientific discipline of a multidisciplinary nature, integrating principles from biomedical engineering as well as from food manufacturing, design and development, i.e., food engineering. An important requirement is also the need to use as little as possible of animal-derived components in the whole CM bioprocess. In this review, we aim to present the current knowledge on different bioengineering aspects, pertinent to different current scientific disciplines but all relevant for CM engineering, relevant for muscle TE, including different cell sources, bioreactor types, media requirements, bioprocess monitoring and kinetics and their modifications for use in CA, all in view of their potential for efficient CM bioprocess scale-up. We believe such a review will offer a good overview of different bioengineering strategies for CM production and will be useful to a range of interested stakeholders, from students just entering the CA field to experienced researchers looking for the latest innovations in the field.

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Section: General Aspects Of Bioreactors For Proliferation and Differe...mentioning

confidence: 99%

Bioengineering Outlook on Cultivated Meat Production

et al. 2022

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“… 27 Rotating‐wall bioreactors provide large surface‐to‐volume ratios, while conveying low shear stresses to the cells due to the horizontal, continuous rotation of the vessel. 23 , 28 Due to the nature of this bioreactor's design, cell harvesting and process monitoring are limited during culturing. A key goal in suspension growth with bioreactors is to obtain homogeneous aggregate growth, but aggregates of limited size.…”

Section: Current Platforms and Their Challengesmentioning

confidence: 99%

“…The high shear forces instigated by these movements can cause smaller hPSC aggregates, affecting their pluripotency and viability 27 . Rotating‐wall bioreactors provide large surface‐to‐volume ratios, while conveying low shear stresses to the cells due to the horizontal, continuous rotation of the vessel 23,28 . Due to the nature of this bioreactor's design, cell harvesting and process monitoring are limited during culturing.…”

Section: Current Platforms and Their Challengesmentioning

confidence: 99%

Advances in hPSC expansion towards therapeutic entities: A review

Tannenbaum

Reubinoff

2022

Cell Proliferation

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For use in regenerative medicine, large‐scale manufacturing of human pluripotent stem cells (hPSCs) under current good manufacturing practice (cGMPs) is required. Much progress has been made since culturing under static two‐dimensional (2D) conditions on feeders, including feeder‐free cultures, conditioned and xeno‐free media, and three‐dimensional (3D) dynamic suspension expansion. With the advent of horizontal‐blade and vertical‐wheel bioreactors, scale‐out for large‐scale production of differentiated hPSCs became possible; control of aggregate size, shear stress, fluid hydrodynamics, batch‐feeding strategies, and other process parameters became a reality. Moving from substantially manipulated processes (i.e., 2D) to more automated ones allows easer compliance to current good manufacturing practices (cGMPs), and thus easier regulatory approval. Here, we review the current advances in the field of hPSC culturing, advantages, and challenges in bioreactor use, and regulatory areas of concern with respect to these advances. Manufacturing trends to reduce risk and streamline large‐scale manufacturing will bring about easier, faster regulatory approval for clinical applications.

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“…This means that, whenever favorable, novel manufacturing strategies and elements with the potential to either reduce bioprocess complexity or increase product quality should be adopted [ 15 ]. A prime example of this is the transition from planar culture formats, ubiquitous in laboratory settings and thus likely to be used in the early stages of development, to automated bioreactor culture, so as to benefit from improved scalability, integrated manufacturing and increased cell quality [ 25 , 26 ]. Other sources of innovation include the development of less costly and more rigorously defined culture media [ 27 ], ingenious cell purification methods [ 28 ] and streamlined cell characterization techniques [ 29 ].…”

Section: Development Of Bioprocesses For Stem Cell Therapy Productsmentioning

confidence: 99%

Bioprocess Economic Modeling: Decision Support Tools for the Development of Stem Cell Therapy Products

et al. 2022

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Over recent years, the field of cell and gene therapy has witnessed rapid growth due to the demonstrated benefits of using living cells as therapeutic agents in a broad range of clinical studies and trials. Bioprocess economic models (BEMs) are fundamental tools for guiding decision-making in bioprocess design, being capable of supporting process optimization and helping to reduce production costs. These tools are particularly important when it comes to guiding manufacturing decisions and increasing the likelihood of market acceptance of cell-based therapies, which are often cost-prohibitive because of high resource and quality control costs. Not only this, but the inherent biological variability of their underlying bioprocesses makes them particularly susceptible to unforeseen costs arising from failed or delayed production batches. The present work reviews important concepts concerning the development of bioprocesses for stem cell therapy products and highlights the valuable role which BEMs can play in this endeavor. Additionally, some theoretical concepts relevant to the building and structuring of BEMs are explored. Finally, a comprehensive review of the existent BEMs so far reported in the scientific literature for stem cell-related bioprocesses is provided to showcase their potential usefulness.

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Single-Use Bioreactors for Human Pluripotent and Adult Stem Cells: Towards Regenerative Medicine Applications

Cited by 18 publications

References 129 publications

Bioengineering Outlook on Cultivated Meat Production

Bioengineering Outlook on Cultivated Meat Production

Advances in hPSC expansion towards therapeutic entities: A review

Bioprocess Economic Modeling: Decision Support Tools for the Development of Stem Cell Therapy Products

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