Improving wave-induced motion bioreactor performance for human mesenchymal stromal cell expansion

Silva, Juliana de Sá da; Mizukami, Amanda; Gil, Laura Pérez; Campos, Jessica Valéria de; Assis, O. B. G.; Covas, Dimas Tadeu; Swiech, Kamilla; Suazo, Cláudio Alberto Torres

doi:10.1016/j.procbio.2019.06.004

Cited by 15 publications

(7 citation statements)

References 32 publications

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“…Although only a small population of cells are exposed to the localized high shear stress and the volume-weighted mean of shear stress is very low (e.g., 0.0032 Pa at 25 rpm and 0.0067 Pa at 60 rpm), accumulated influence induced by shear stress is still significant on cell growth (Yuan et al, 2014 ; Jossen et al, 2016 ). Accordingly, alternative bioreactor designs have been developed to provide a low-shear stress environment, such as WAVE Bioreactor™ (GE Healthcare), BIOSTAT® CultiBag RM bioreactor (Sartorius), and Vertical-Wheel™ bioreactor (PBS Biotech) (Timmins et al, 2012 ; Sousa et al, 2015 ; Jossen et al, 2016 ; da Silva et al, 2019 ).…”

Section: The Microenvironment Change In Microcarrier-based Bioreactormentioning

confidence: 99%

Influence of Microenvironment on Mesenchymal Stem Cell Therapeutic Potency: From Planar Culture to Microcarriers

Tsai

Jeske

Chen

et al. 2020

Front. Bioeng. Biotechnol.

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Human mesenchymal stem cells (hMSCs) are a promising candidate in cell therapy as they exhibit multilineage differentiation, homing to the site of injury, and secretion of trophic factors that facilitate tissue healing and/or modulate immune response. As a result, hMSC-derived products have attracted growing interests in preclinical and clinical studies. The development of hMSC culture platforms for large-scale biomanufacturing is necessary to meet the requirements for late-phase clinical trials and future commercialization. Microcarriers in stirred-tank bioreactors have been widely utilized in large-scale expansion of hMSCs for translational applications because of a high surface-to-volume ratio compared to conventional 2D planar culture. However, recent studies have demonstrated that microcarrier-expanded hMSCs differ from dish-or flask-expanded cells in size, morphology, proliferation, viability, surface markers, gene expression, differentiation potential, and secretome profile which may lead to altered therapeutic potency. Therefore, understanding the bioprocessing parameters that influence hMSC therapeutic efficacy is essential for the optimization of microcarrier-based bioreactor system to maximize hMSC quantity without sacrificing quality. In this review, biomanufacturing parameters encountered in planar culture and microcarrier-based bioreactor culture of hMSCs are compared and discussed with specific focus on cell-adhesion surface (e.g., discontinuous surface, underlying curvature, microcarrier stiffness, porosity, surface roughness, coating, and charge) and the dynamic microenvironment in bioreactor culture (e.g., oxygen and nutrients, shear stress, particle collision, and aggregation). The influence of dynamic culture in bioreactors on hMSC properties is also reviewed in order to establish connection between bioprocessing and stem cell function. This review addresses fundamental principles and concepts for future design of biomanufacturing systems for hMSCbased therapy.

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Section: The Microenvironment Change In Microcarrier-based Bioreactormentioning

confidence: 99%

Influence of Microenvironment on Mesenchymal Stem Cell Therapeutic Potency: From Planar Culture to Microcarriers

Tsai

Jeske

Chen

et al. 2020

Front. Bioeng. Biotechnol.

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“…To bypass the potential for shear stress, other bioreactor types, including fixed-bed bioreactors, hollow fiber bioreactors and wave motion bioreactors, have also been used to expand hMSCs [26,44,71,72]. Microcarrier suspensions in wave bioreactors have demonstrated significantly lower shear stress [64,73].…”

Section: Mixing (Agitation and Rocking)mentioning

confidence: 99%

“…There are two ways to regulate the temperature in bioreactor culture. One is to maintain the temperature of the water jacket of the bioreactor [40,71] or the metal plate attached to the bioreactor bag [44,74] while the other is directly to control the temperature of the bulk culture by measuring the temperature with a thermocouple or a temperature sensor and then to warm the bioreactor with a heating blanket or pad [36,75]. The former may have some deviations due to the indirect measurement while the latter requires more attention to understand the relative locations of the temperature sensor and the heating source.…”

Section: Control System (Temperature and Ph And Do)mentioning

confidence: 99%

“…In general, there are several ways to count cells in microcarrier culture: (1) Cell counting after cells have detached from microcarriers [26,29,37,50]; (2) Cell counting after microcarriers have dissolved [35,46,48]; (3) Nuclei counting after cells lysis with microcarriers [27,28,36]; (4) DNA quantification [18,29]; (5) Metabolic assays [34,44,47,91]. Counting methods with simple steps and high throughput are ideal and more favorable than assaybased approaches.…”

Section: Sampling and Cell Countingmentioning

confidence: 99%

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Bioprocessing of Human Mesenchymal Stem Cells: From Planar Culture to Microcarrier-Based Bioreactors

Tsai

Pacak

2021

Bioengineering

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Human mesenchymal stem cells (hMSCs) have demonstrated great potential to be used as therapies for many types of diseases. Due to their immunoprivileged status, allogeneic hMSCs therapies are particularly attractive options and methodologies to improve their scaling and manufacturing are needed. Microcarrier-based bioreactor systems provide higher volumetric hMSC production in automated closed systems than conventional planar cultures. However, more sophisticated bioprocesses are necessary to successfully convert from planar culture to microcarriers. This article summarizes key steps involved in the planar culture to microcarrier hMSC manufacturing scheme, from seed train, inoculation, expansion and harvest. Important bioreactor parameters, such as temperature, pH, dissolved oxygen (DO), mixing, feeding strategies and cell counting techniques, are also discussed.

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“…The adhesion phase was first performed in spinner flasks, then in the modified Cellbags in dynamic conditions, and in static with reduced volume. The latter conditions led to the best overall cell expansion, with a final yield of 2.56 × 10 8 UCM–hMSCs in 600 mL [ 59 ]. The same group then compared the expansion of these cells in the modified Cellbags (600 mL working volume) and 500 mL spinner flasks.…”

Section: Single-use Bioreactors For Stem Cell Biomanufacturingmentioning

confidence: 99%

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

Rodrigues

2021

Bioengineering

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Research on human stem cells, such as pluripotent stem cells and mesenchymal stromal cells, has shown much promise in their use for regenerative medicine approaches. However, their use in patients requires large-scale expansion systems while maintaining the quality of the cells. Due to their characteristics, bioreactors have been regarded as ideal platforms to harbour stem cell biomanufacturing at a large scale. Specifically, single-use bioreactors have been recommended by regulatory agencies due to reducing the risk of product contamination, and many different systems have already been developed. This review describes single-use bioreactor platforms which have been used for human stem cell expansion and differentiation, along with their comparison with reusable systems in the development of a stem cell bioprocess for clinical applications.

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Improving wave-induced motion bioreactor performance for human mesenchymal stromal cell expansion

Cited by 15 publications

References 32 publications

Influence of Microenvironment on Mesenchymal Stem Cell Therapeutic Potency: From Planar Culture to Microcarriers

Influence of Microenvironment on Mesenchymal Stem Cell Therapeutic Potency: From Planar Culture to Microcarriers

Bioprocessing of Human Mesenchymal Stem Cells: From Planar Culture to Microcarrier-Based Bioreactors

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

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