Stem cell cultivation in bioreactors

Rodrigues, Carlos Alberto Chirano; Fernandes, Tiago G.; Diogo, Maria Margarida; Silva, Cláudia Lobato da; Cabral, Joaquim M. S.

doi:10.1016/j.biotechadv.2011.06.009

Cited by 185 publications

(164 citation statements)

References 202 publications

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“…Afterwards, the process system can be designed, the strategy for quality assurance can be developed and the methods for process monitoring can be defined. Then the actual production process could be established by development of routine and reproducibility [19].…”

Section: Process Requirements For Stem Cell Expansionmentioning

confidence: 99%

“…However, these culture vessels offer a limited scale-up potential and little possibilities for process control and cannot be automated easily. Furthermore, the process monitoring of these systems requires sampling, which endangers the system sterility [19]. In terms of cell characterization, these systems enable an easy determination of growth rate and metabolite kinetics because of simple sampling of media and cell detachment for cell count measurements.…”

Section: Expansion Of Hmsc In Static Systemsmentioning

confidence: 99%

“…The cultivation of hMSC is typically performed statically in standard systems like tissue culture flasks, culture trays, roller bottles, gas permeable blood bags or multi-well plates [19,40,41]. These mostly sterile disposable systems contain standard plastic surfaces.…”

Section: Expansion Of Hmsc In Static Systemsmentioning

confidence: 99%

See 2 more Smart Citations

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

Cierpka

Elseberg

Niss³

et al. 2012

Chemie Ingenieur Technik

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Reactor concepts for human mesenchymal stem cell (hMSC) production are introduced. Thereby, special interest is laid on the realization of these concepts as disposables fulfilling the GMP and PAT requirements. The specialty of the hMSC production process is the cell itself being the product. This results in completely different process requirements compared to e.g. protein production in mammalian cells. Thus, great attention has to be given to the shear sensitivity of the cells. The cultivation and the harvest of the cells have to be very gentle to neither influence cell viability nor cell differentiability. Further, the production process should not cause any undesirable cell changes. For hMSC production, cell harvest is the main challenging process step. The reactor concepts should be suitable for hMSC production for clinical trials as ATMPs. Therefore, disposable systems are especially applicable. The review describes more detailed bone marrow-derived hMSC production in a disposable stirred tank reactor as promising reactor concept.

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Section: Process Requirements For Stem Cell Expansionmentioning

confidence: 99%

Section: Expansion Of Hmsc In Static Systemsmentioning

confidence: 99%

See 1 more Smart Citation

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

Cierpka

Elseberg

Niss³

et al. 2012

Chemie Ingenieur Technik

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“…[3][4][5] The integration of bioreactor systems in current laboratory-scale processes therefore holds promise for the translation in a clinical and ultimately commercial setting. 6,7 Bioreactors have been employed frequently to provide sufficient nutrient and oxygen transport and removal of waste products 6,[8][9][10][11][12] while allowing for monitoring and control of physicochemical and biological parameters 7,[13][14][15][16][17] during cell proliferation, differentiation, and the development of cell-carrier constructs. Furthermore, these parameters could be used as nondestructive quality indicators of the cells or the developing construct.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Validation of the Presto Blue™ Metabolic Assay for Online Monitoring of Cell Proliferation in a 3D Perfusion Bioreactor System

Sonnaert

Papantoniou

Luyten

et al. 2015

Tissue Engineering Part C: Methods

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As the fields of tissue engineering and regenerative medicine mature toward clinical applications, the need for online monitoring both for quantitative and qualitative use becomes essential. Resazurin-based metabolic assays are frequently applied for determining cytotoxicity and have shown great potential for monitoring 3D bioreactor-facilitated cell culture. However, no quantitative correlation between the metabolic conversion rate of resazurin and cell number has been defined yet. In this work, we determined conversion rates of Presto BlueÔ, a resazurin-based metabolic assay, for human periosteal cells during 2D and 3D static and 3D perfusion cultures. Our results showed that for the evaluated culture systems there is a quantitative correlation between the Presto Blue conversion rate and the cell number during the expansion phase with no influence of the perfusion-related parameters, that is, flow rate and shear stress. The correlation between the cell number and Presto Blue conversion subsequently enabled the definition of operating windows for optimal signal readouts. In conclusion, our data showed that the conversion of the resazurin-based Presto Blue metabolic assay can be used as a quantitative readout for online monitoring of cell proliferation in a 3D perfusion bioreactor system, although a system-specific validation is required.

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“…Although many experiments and theories have shown that the functionality and quality of cultured cells and engineered tissues in bioreactors can be improved by mechanical stimulation, research on the direct impact of mechanical stimulation on cells or tissues, such as the magnitude, frequency, continuity, and cyclical changes of the mechanical stimuli, are not well characterized (Yeatts & Fisher 2011;Yu et al 2004;Martin et al 2004;Song et al 2006;Hu and Athanasiou 2005;Massimo et al 2004;Van Dyke et al 2012). In addition, in the culture suspension, collisions with the inner and outer walls of bioreactors are inevitable especially when the density and dimensions of the cell-scaffold constructs, such as those observed in the RWVB (rotating wall vessel bioreactor), reach a certain level (Song et al 2011;Rodrigues et al 2011;Song et al 2008). Such collisions could cause shear stresses that may be destructive to the cells in the engineered tissue.…”

Section: Introductionmentioning

confidence: 99%

Numerical simulation of fluid field and in vitro three-dimensional fabrication of tissue-engineered bones in a rotating bioreactor and in vivo implantation for repairing segmental bone defects

Song

Wang

Zhang

et al. 2013

Cell Stress and Chaperones

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In this paper, two-dimensional flow field simulation was conducted to determine shear stresses and velocity profiles for bone tissue engineering in a rotating wall vessel bioreactor (RWVB). In addition, in vitro three-dimensional fabrication of tissue-engineered bones was carried out in optimized bioreactor conditions, and in vivo implantation using fabricated bones was performed for segmental bone defects of Zelanian rabbits. The distribution of dynamic pressure, total pressure, shear stress, and velocity within the culture chamber was calculated for different scaffold locations. According to the simulation results, the dynamic pressure, velocity, and shear stress around the surface of cell-scaffold construction periodically changed at different locations of the RWVB, which could result in periodical stress stimulation for fabricated tissue constructs. However, overall shear stresses were relatively low, and the fluid velocities were uniform in the bioreactor. Our in vitro experiments showed that the number of cells cultured in the RWVB was five times higher than those cultured in a T-flask. The tissue-engineered bones grew very well in the RWVB. This study demonstrates that stress stimulation in an RWVB can be beneficial for cell/bio-derived bone constructs fabricated in an RWVB, with an application for repairing segmental bone defects.

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Stem cell cultivation in bioreactors

Cited by 185 publications

References 202 publications

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

Quantitative Validation of the Presto Blue™ Metabolic Assay for Online Monitoring of Cell Proliferation in a 3D Perfusion Bioreactor System

Numerical simulation of fluid field and in vitro three-dimensional fabrication of tissue-engineered bones in a rotating bioreactor and in vivo implantation for repairing segmental bone defects

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