Scalable culture of human induced pluripotent cells on microcarriers under xeno-free conditions using single-use vertical-wheel (TM) bioreactors

摘要

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 CONCLUSION 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 x 10(6) cells mL(-1) and volumetric productivities of 2.01 +/- 0.04 x 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. 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. (c) 2018 Society of Chemical Industry