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Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: Growth behavior of human adipose tissue-derived stromal/stem cells at small scale : numerical and experimental investigations
Authors: Jossen, Valentin
Eibl-Schindler, Regine
Kraume, Matthias
Eibl, Dieter
et. al: No
DOI: 10.3390/bioengineering5040106
Published in: Bioengineering
Volume(Issue): 5
Issue: 4
Pages: 106
Issue Date: 4-Dec-2018
Publisher / Ed. Institution: MDPI
ISSN: 2306-5354
Language: English
Subjects: Euler–Euler and Euler–Lagrange approaches; Computational fluid dynamics; Human adipose tissue-derived stromal/stem cells; Humane telomerase reversed transcriptase immortalized hASCs; Microcarrier; Particle image velocimetry/shadowgraphy measurements; Segregated growth model
Subject (DDC): 660.6: Biotechnology
Abstract: Human adipose tissue-derived stromal/stem cells (hASCs) are a valuable source of cells for clinical applications, especially in the field of regenerative medicine. Therefore, it comes as no surprise that the interest in hASCs has greatly increased over the last decade. However, in order to use hASCs in clinically relevant numbers, in vitro expansion is required. Single-use stirred bioreactors in combination with microcarriers (MCs) have shown themselves to be suitable systems for this task. However, hASCs tend to be less robust, and thus, more shear sensitive than conventional production cell lines for therapeutic antibodies and vaccines (e.g., Chinese Hamster Ovary cells CHO, Baby Hamster Kidney cells BHK), for which these bioreactors were originally designed. Hence, the goal of this study was to investigate the influence of different shear stress levels on the growth of humane telomerase reversed transcriptase immortalized hASCs (hTERT-ASC) and aggregate formation in stirred single-use systems at the mL scale: the 125 mL (= SP100) and the 500 mL (= SP300) disposable Corning® spinner flask. Computational fluid dynamics (CFD) simulations based on an Euler⁻Euler and Euler⁻Lagrange approach were performed to predict the hydrodynamic stresses (0.06⁻0.87 Pa), the residence times (0.4⁻7.3 s), and the circulation times (1.6⁻16.6 s) of the MCs in different shear zones for different impeller speeds and the suspension criteria (Ns1u, Ns1). The numerical findings were linked to experimental data from cultivations studies to develop, for the first time, an unstructured, segregated mathematical growth model for hTERT-ASCs. While the 125 mL spinner flask with 100 mL working volume (SP100) provided up to 1.68.10⁵ hTERT-ASC/cm² (= 0.63 × 10⁶ living hTERT-ASCs/mL, EF 56) within eight days, the peak living cell density of the 500 mL spinner flask with 300 mL working volume (SP300) was 2.46 × 10⁵ hTERT-ASC/cm² (= 0.88 × 10⁶ hTERT-ASCs/mL, EF 81) and was achieved on day eight. Optimal cultivation conditions were found for Ns1u < N < Ns1, which corresponded to specific power inputs of 0.3⁻1.1 W/m³. The established growth model delivered reliable predictions for cell growth on the MCs with an accuracy of 76⁻96% for both investigated spinner flask types.
Fulltext version: Published version
License (according to publishing contract): CC BY 4.0: Attribution 4.0 International
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Appears in Collections:Publikationen Life Sciences und Facility Management

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