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Scalable culture of human induced pluripotent cells on microcarriers under xeno‐free conditions using single‐use vertical‐wheel™ bioreactors
Author(s) -
Rodrigues Carlos AV,
Silva Teresa P,
Nogueira Diogo ES,
Fernandes Tiago G,
Hashimura Yas,
Wesselschmidt Robin,
Diogo Maria Margarida,
Lee Brian,
Cabral Joaquim MS
Publication year - 2018
Publication title -
journal of chemical technology and biotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.64
H-Index - 117
eISSN - 1097-4660
pISSN - 0268-2575
DOI - 10.1002/jctb.5738
Subject(s) - microcarrier , bioreactor , induced pluripotent stem cell , regenerative medicine , scalability , human induced pluripotent stem cells , laboratory flask , cell culture , computer science , biochemical engineering , biomedical engineering , process engineering , chemistry , stem cell , microbiology and biotechnology , engineering , biology , genetics , embryonic stem cell , operating system , organic chemistry , gene
BACKGROUND Human induced pluripotent stem cells (hiPSC) are expected to become powerful tools for disease modelling, for the discovery and testing of new drugs and, ultimately, for regenerative therapies. The success of these applications depends on the development of scalable bioprocesses capable of generating large numbers of hiPSC and derivatives. RESULTS In this work, the novel vertical‐wheel single‐use bioreactors were used for the first time for the expansion of hiPSC under xeno‐free conditions. Cultures were performed on microcarriers in two different scales of vessels (100 and 500 mL with 80 and 300 mL working volumes, respectively), leading to maximum cell densities up to 1.21 ± 0.02 × 10 6 cells mL −1 and volumetric productivities of 2.01 ± 0.04 × 10 5 cells mL −1 day −1 . The pluripotency as well as a normal karyotype were maintained after cell expansion. Consistency of the processes was confirmed with a different hiPSC line, which is an important aspect for a personalized medicine approach. CONCLUSION The results here described demonstrate the feasibility of scalable production of hiPSC in a microcarrier‐based system using vertical‐wheel bioreactors. The protocols developed in this study provide a Good Manufacturing Practices (GMP)‐compliant system for hiPSC manufacturing which may be an important step towards the successful implementation of hiPSC‐based products. © 2018 Society of Chemical Industry