Online- and offline- monitoring of stem cell expansion on microcarrier

Justice, C.; Leber, Jasmin; Freimark, Denise; Grace, P. Pino; Kraume, Matthias; Czermak, Peter

doi:10.1007/s10616-011-9359-4

Cited by 33 publications

(32 citation statements)

References 35 publications

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“…For hMSC expansion in particular, the online monitoring of cell growth and viability should be satisfied. For this, the application of dielectric spectroscopy for biomass monitoring has been described in the literature [37].…”

Section: Process Monitoringmentioning

confidence: 99%

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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 Monitoringmentioning

confidence: 99%

“…Two different cultivations are exemplary shown (ᮀ and ). Cell growth was determined offline via a florescence assay [37]. At the end of the cultivation, cells were harvested with an external device using trypsin.…”

Section: Transfer Of Hmsc-tert Production Process In a Disposable Systemmentioning

confidence: 99%

hMSC Production in Disposable Bioreactors with Regards to GMP and PAT

Cierpka

Elseberg

Niss³

et al. 2012

Chemie Ingenieur Technik

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“…Online monitoring tools are ideal, but offline data analysis is needed for correlation. The cell density on a microcarrier is often determined offline by cell lysis followed by counting the released nuclei, but this is rather imprecise [86]. Alternatively, an intercalating fluorescent dye such as SybrGreen I can be used to estimate DNA levels, which are linearly related to the cell density, and this can be achieved without cell detachment [86].…”

Section: Pat Applicationsmentioning

confidence: 99%

“…The cell density on a microcarrier is often determined offline by cell lysis followed by counting the released nuclei, but this is rather imprecise [86]. Alternatively, an intercalating fluorescent dye such as SybrGreen I can be used to estimate DNA levels, which are linearly related to the cell density, and this can be achieved without cell detachment [86]. Dielectric spectroscopy is a promising tool for the online measurement of cell density [21,86,87].…”

Section: Pat Applicationsmentioning

confidence: 99%

The Challenge of Human Mesenchymal Stromal Cell Expansion: Current and Prospective Answers

Elseberg¹,

Leber²,

Weidner³

et al. 2017

New Insights Into Cell Culture Technology

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In the field of cell therapy, allogenic human mesenchymal stromal cells (hMSCs) are often used in clinical trials, creating a demand for cell mass production using efficient dynamic bioreactor systems. As an advanced therapy medicinal product (ATMP), such cells should meet certain special requirements, including product specifications requiring a production process compatible with good manufacturing practice (GMP). The development of processes in which the cells are the product therefore remains a significant challenge. This chapter describes the requirements at different steps in the upstream and downstream phases of such dynamic processes. Potential solutions are presented and future prospects are discussed, including the selection of media and carriers for the strictly adherent growing cells, allowing efficient cell adhesion and detachment. Strategies for dynamic cultivation in bioreactors are described in detail for fixed-bed and stirred-tank reactors based on GMP requirements and the integration of process analytical technology (PAT). Following cell harvest, separation and purification, the formulation and storage of the product are also described. Finally, the chapter covers important cell quality characteristics necessary for the approval of ATMPs.

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“…Thus, dead or leaking cells are not captured by this technology [103]. Additionally, the capacitance signal is reported to be insensitive to gas bubbles and microcarriers facilitating the monitoring of cell culture processes in common sparged as well as fixed bed bioreactors [102,104,105]. However, very high volume fractions of non-biomass materials close to the sensor may influence the capacitance signal since the polarizable cells are replaced by non-polarizable materials [102].…”

Section: Dielectric Spectroscopymentioning

confidence: 99%