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Breanna S. Borys

Bio: Breanna S. Borys is an academic researcher from University of Calgary. The author has contributed to research in topics: Induced pluripotent stem cell & Embryonic stem cell. The author has an hindex of 7, co-authored 12 publications receiving 89 citations.

Papers
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Journal ArticleDOI
TL;DR: It is demonstrated that a vertical‐wheel bioreactor‐based bioprocess can provide optimal conditions for efficient, rapid generation of high‐quality hiPSCs to meet the demands for clinical manufacturing of therapeutic cell products.
Abstract: Human induced pluripotent stem cells (hiPSCs) have generated a great deal of attention owing to their capacity for self-renewal and differentiation into the three germ layers of the body. Their discovery has facilitated a new era in biomedicine for understanding human development, drug screening, disease modeling, and cell therapy while reducing ethical issues and risks of immune rejection associated with traditional embryonic stem cells. Bioreactor-based processes have been the method of choice for the efficient expansion and differentiation of stem cells in controlled environments. Current protocols for the expansion of hiPSCs use horizontal impeller, paddle, or rocking wave mixing method bioreactors which require large static cell culture starting populations and achieve only moderate cell fold increases. This study focused on optimizing inoculation, agitation, oxygen, and nutrient availability for the culture of hiPSCs as aggregates in single-use, low-shear, vertical-wheel bioreactors. Under optimized conditions, we achieved an expansion of more than 30-fold in 6 days using a small starting population of cells and minimal media resources throughout. Importantly, we showed that that this optimized bioreactor expansion protocol could be replicated over four serial passages resulting in a cumulative cell expansion of 1.06E6-fold in 28 days. Cells from the final day of the serial passage were of high quality, maintaining a normal karyotype, pluripotent marker staining, and the ability to form teratomas in vivo. These findings demonstrate that a vertical-wheel bioreactor-based bioprocess can provide optimal conditions for efficient, rapid generation of high-quality hiPSCs to meet the demands for clinical manufacturing of therapeutic cell products.

29 citations

Journal ArticleDOI
TL;DR: It is determined that if the volume average energy dissipation rate or maximum shear stress were kept constant, aggregate sizes could be maintained through scale-up and scale- up stem cell growth efficiently without extensive testing of bioreactor agitation rates.

28 citations

Journal ArticleDOI
TL;DR: A CFD model developed to determine the effects of average shear rates and turbulent eddies on the formation and growth of murine embryonic stem cell aggregates found a correlation between average eddy size and aggregate size, which depended on bioreactor agitation rates.

17 citations

Journal ArticleDOI
TL;DR: It is concluded that automated bioreactor processing could be used to efficiently generate large numbers of autologous DSCs while maintaining their inherent regenerative function.
Abstract: Endogenous dermal stem cells (DSCs) reside in the adult hair follicle mesenchyme and can be isolated and grown in vitro as self-renewing colonies called skin-derived precursors (SKPs). Following transplantation into skin, SKPs can generate new dermis and reconstitute the dermal papilla and connective tissue sheath, suggesting they could have important therapeutic value for the treatment of skin disease (alopecia) or injury. Controlled cell culture processes must be developed to efficiently and safely generate sufficient stem cell numbers for clinical use. Compared with static culture, stirred-suspension bioreactors generated fivefold greater expansion of viable SKPs. SKPs from each condition were able to repopulate the dermal stem cell niche within established hair follicles. Both conditions were also capable of inducing de novo hair follicle formation and exhibited bipotency, reconstituting the dermal papilla and connective tissue sheath, although the efficiency was significantly reduced in bioreactor-expanded SKPs compared with static conditions. We conclude that automated bioreactor processing could be used to efficiently generate large numbers of autologous DSCs while maintaining their inherent regenerative function. Stem Cells Translational Medicine 2017;6:434-443.

14 citations


Cited by
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Journal ArticleDOI
02 Sep 2020
TL;DR: Digital twins (DTs) as discussed by the authors are virtual constructs of physical systems that mirror the behavior and dynamics of such physical systems, and are used in various processes and product industries to facilitate the transformation of the manufacturing sector to a more agile and intelligent one.
Abstract: The development and application of emerging technologies of Industry 4.0 enable the realization of digital twins (DT), which facilitates the transformation of the manufacturing sector to a more agile and intelligent one. DTs are virtual constructs of physical systems that mirror the behavior and dynamics of such physical systems. A fully developed DT consists of physical components, virtual components, and information communications between the two. Integrated DTs are being applied in various processes and product industries. Although the pharmaceutical industry has evolved recently to adopt Quality-by-Design (QbD) initiatives and is undergoing a paradigm shift of digitalization to embrace Industry 4.0, there has not been a full DT application in pharmaceutical manufacturing. Therefore, there is a critical need to examine the progress of the pharmaceutical industry towards implementing DT solutions. The aim of this narrative literature review is to give an overview of the current status of DT development and its application in pharmaceutical and biopharmaceutical manufacturing. State-of-the-art Process Analytical Technology (PAT) developments, process modeling approaches, and data integration studies are reviewed. Challenges and opportunities for future research in this field are also discussed.

84 citations

Journal ArticleDOI
TL;DR: This work critically review the state of the art and future trends of biomaterial microparticles in contact with cells and tissues, excluding internalization studies, and with emphasis on innovative particle design and applications.

70 citations

Posted ContentDOI
25 Aug 2020-bioRxiv
TL;DR: The density and dynamic viscosity of DMEM and RPMI-1640 media supplemented with typical concentrations of foetal bovine serum were measured to serve as a reference for computational design analysis and demonstrated clear differences in maximum wall shear stress and pressure between fluid models.
Abstract: Culture medium is frequently modelled as water in computational fluid dynamics (CFD) analysis of in vitro culture systems involving flow, such as bioreactors and organ-on-chips. However, culture medium can be expected to have different properties to water due to its higher solute content. Furthermore, cellular activities such as metabolism and secretion of ECM proteins alter the composition of culture medium and therefore its properties during culture. As these properties directly determine the hydromechanical stimuli exerted on cells in vitro, these, along with any changes during culture must be known for CFD model accuracy and meaningful interpretation of cellular responses. In this study, the density and dynamic viscosity of DMEM and RPMI-1640 media supplemented with typical concentrations of foetal bovine serum (0, 5, 10 and 20% v/v) were measured to serve as a reference for computational design analysis. Changes in these properties during culture was investigated with H460 and HN6 cell lines. The density and dynamic viscosity of the media increased proportional to the % volume of added foetal bovine serum (FBS). Importantly, the viscosity of 5% FBS-supplemented RPMI-1640 was shown to increase significantly after 3 days of culture of NCI-H460 and HN6 cell lines, with distinct differences between magnitude of change for each cell line. Finally, measured values were applied in CFD analysis of a simple microfluidic device, which demonstrated clear differences in maximum wall shear stress and pressure between fluid models. Overall, these results highlight the importance of characterizing model-specific properties for CFD design analysis of cell culture systems.

65 citations

Journal ArticleDOI
TL;DR: The factors driving concerted research endeavors in each of the main classes of bioreactors are briefly examined and the major advancements that have been reported in the last three years are described.
Abstract: Bioreactors have become indispensable tools in the cell-based therapy industry. Various forms of bioreactors are used to maintain well-controlled microenvironments to regulate cell growth, differentiation, and tissue development. They are essential for providing standardized, reproducible cell-based products for regenerative medicine applications or to establish physiologically relevant in vitro models for testing of pharmacologic agents. In this review, we discuss three main classes of bioreactors: cell expansion bioreactors, tissue engineering bioreactors, and lab-on-a-chip systems. We briefly examine the factors driving concerted research endeavors in each of these areas and describe the major advancements that have been reported in the last three years. Emerging issues that impact the commercialization and clinical use of bioreactors include (i) the need to scale up to greater cell quantities and larger graft sizes, (ii) simplification of in vivo systems to function without exogenous stem cells or growth factors or both, and (iii) increased control in the manufacture and monitoring of miniaturized systems to better capture complex tissue and organ physiology.

57 citations

Journal ArticleDOI
TL;DR: The hair follicle (HF) is a highly conserved sensory organ associated with the immune response against pathogens, thermoregulation, sebum production, angiogenesis, neurogenesis and wound healing as discussed by the authors.
Abstract: The hair follicle (HF) is a highly conserved sensory organ associated with the immune response against pathogens, thermoregulation, sebum production, angiogenesis, neurogenesis and wound healing. Although recent advances in lineage-tracing techniques and the ability to profile gene expression in small populations of cells have increased the understanding of how stem cells operate during hair growth and regeneration, the construction of functional follicles with cycling activity is still a great challenge for the hair research field and for translational and clinical applications. Given that hair formation and cycling rely on tightly coordinated epithelial–mesenchymal interactions, we thus review potential cell sources with HF-inducive capacities and summarize current bioengineering strategies for HF regeneration with functional restoration.

52 citations