Next Article in Journal
Detection of Osteoporosis from Percussion Responses Using an Electronic Stethoscope and Machine Learning
Previous Article in Journal
Predicting the Biodegradation of Magnesium Alloy Implants: Modeling, Parameter Identification, and Validation
Article Menu
Issue 4 (December) cover image

Export Article

Open AccessArticle
Bioengineering 2018, 5(4), 106; https://doi.org/10.3390/bioengineering5040106

Growth Behavior of Human Adipose Tissue-Derived Stromal/Stem Cells at Small Scale: Numerical and Experimental Investigations

1
Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, 8820 Wädenswil, Switzerland
2
Department of Process Engineering, Technical University of Berlin, 10623 Berlin, Germany, [email protected]
*
Author to whom correspondence should be addressed.
Received: 6 November 2018 / Revised: 23 November 2018 / Accepted: 30 November 2018 / Published: 4 December 2018
(This article belongs to the Special Issue Advanced Dynamic Cell and Tissue Culture, Volume 2)
Full-Text   |   PDF [16401 KB, uploaded 13 December 2018]   |  

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. View Full-Text
Keywords: computational fluid dynamics; human adipose tissue-derived stromal/stem cells; humane telomerase reversed transcriptase immortalized hASCs; microcarrier; segregated growth model; Euler–Euler and Euler–Lagrange approaches; particle image velocimetry/shadowgraphy measurements computational fluid dynamics; human adipose tissue-derived stromal/stem cells; humane telomerase reversed transcriptase immortalized hASCs; microcarrier; segregated growth model; Euler–Euler and Euler–Lagrange approaches; particle image velocimetry/shadowgraphy measurements
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Jossen, V.; Eibl, R.; Kraume, M.; Eibl, D. Growth Behavior of Human Adipose Tissue-Derived Stromal/Stem Cells at Small Scale: Numerical and Experimental Investigations. Bioengineering 2018, 5, 106.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Bioengineering EISSN 2306-5354 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top