A new perfusion mode of culture for WJ‐MSCs expansion in a stirred and online monitored bioreactor

Autor: Bruno Ebel, Emmanuel Guedon, Fanny Gallo, Eric Olmos, Caroline Sion, Natalia de Isla, Dima Ghannoum, Isabelle Chevalot
Přispěvatelé: Laboratoire Réactions et Génie des Procédés (LRGP), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Biotechnology and Bioengineering
Biotechnology and Bioengineering, Wiley, 2021, 118 (11), pp.4453-4464. ⟨10.1002/bit.27914⟩
ISSN: 0006-3592
1097-0290
DOI: 10.1002/bit.27914⟩
Popis: Since a clinical dose requires a minimum of 106 cells per kilogram of patients, it is therefore crucial to develop a scalable method of production of Wharton Jelly Mesenchymal stem cells (WJ-MSCs) with maintained inner characteristics. Scalable expansion of WJ-MSCs on microcarriers usually found in cell culture, involved specific cell detachment using trypsin, and could have harmful effects on cells. In this work, performance of batch, fed-batch and perfused-continuous mode of culture were compared. The batch and fed-batch modes resulted in expansion factors of 5 and 43, respectively. The perfused-continuous mode strategy consisted in the implementation of a settling tube inside the bioreactor. The diameter of the tube was calculated to maintain microcarriers colonized by cells in the bioreactor whereas empty microcarriers (responsible of potentially damaging collisions) were removed, using a continuous flow rate based on MSCs physiological requirements. Thanks to this strategy, a maximal number of 800 million of cells was obtained in a 1.5 L bioreactor in 10 days. Lastly, on-line dielectric spectroscopy was implemented in the bioreactor and indicated that cell growth could be monitored during the culture. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE