Open AccessScale‐up of adipose tissue‐derived mesenchymal stem cell production in stirred single‐use bioreactors under low‐serum conditions
Author(s) -
Schirmaier Carmen,
Jossen Valentin,
Kaiser Stephan C.,
Jüngerkes Frank,
Brill Silke,
SafaviNab Agnieszka,
Siehoff Ann,
Bos Christian,
Eibl Dieter,
Eibl Regine
Publication year - 2014
Publication title -
engineering in life sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.547
H-Index - 57
eISSN - 1618-2863
pISSN - 1618-0240
DOI - 10.1002/elsc.201300134
Subject(s) - microcarrier , bioreactor , mesenchymal stem cell , microscale chemistry , scale up , impeller , suspension (topology) , adipose tissue , tissue engineering , biomedical engineering , materials science , chemistry , biology , cell , microbiology and biotechnology , engineering , mathematics , mechanical engineering , biochemistry , physics , mathematics education , organic chemistry , classical mechanics , homotopy , pure mathematics
Suspension cultures, in which human mesenchymal stem cells are cultivated on microcarriers in scalable single‐use stirred bioreactor types, have been shown to be a promising alternative to planar flask cultures. However, stirred single‐use bioreactors were originally developed for production processes with robust, permanent cell lines. Human mesenchymal stem cells are adherent primary cells and thus expanding them in such bioreactor systems imposes more stringent requirements on bioreactor systems. For low‐serum conditions (5%) and different types of stirred single‐use bioreactors, a suspension criteria‐based approach for expanding human adipose tissue‐derived mesenchymal stem cells (hASCs) from milliliter to pilot scale was successfully developed. For process scale‐up, experimental and numerical investigations were performed to (i) predict optimum impeller speeds, (ii) determine the main engineering parameters (local shear stress, turbulent dissipation rate, Kolmogorov microscale), and (iii) verify suspension criteria N S1 and N S1u for rapid process transfer from 100 mL to 2 L and 35 L cultures. Using optimized medium‐microcarrier combinations as well as N S1 and N S1u as scale‐up factors, total hASC quantities between 3 × 10 7 (100 mL scale) and 1 × 10 10 (35 L scale) were obtained. The cell quantities obtained are the highest reported to date for scalable single‐use bioreactors under low‐serum conditions.