title: Scalable microcarrier-based manufacturing of mesenchymal stem/stromal cells.
abstract: Due to their unique features, mesenchymal stem/stromal cells (MSC) have been exploited in clinical settings as therapeutic candidates for the treatment of a variety of diseases. However, the success in obtaining clinically-relevant MSC numbers for cell-based therapies is dependent on efficient isolation and ex vivo expansion protocols, able to comply with good manufacturing practices (GMP). In this context, the 2-dimensional static culture systems typically used for the expansion of these cells present several limitations that may lead to reduced cell numbers and compromise cell functions. Furthermore, many studies in the literature report the expansion of MSC using fetal bovine serum (FBS)-supplemented medium, which has been critically rated by regulatory agencies. Alternative platforms for the scalable manufacturing of MSC have been developed, namely using microcarriers in bioreactors, with also a considerable number of studies now reporting the production of MSC using xenogeneic/serum-free medium formulations. In this review we provide a comprehensive overview on the scalable manufacturing of human mesenchymal stem/stromal cells, depicting the various steps involved in the process from cell isolation to ex vivo expansion, using different cell tissue sources and culture medium formulations and exploiting bioprocess engineering tools namely microcarrier technology and bioreactors.
authors.affiliation: Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa, Portugal.
authors.forename: António M
authors.initials: AM
authors.lastname: de Soure
authors.affiliation: Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandes-Platzgummer
authors.affiliation: Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa, Portugal.
authors.forename: Cláudia L
authors.initials: CL
authors.lastname: da Silva
authors.affiliation: Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa, Portugal. Electronic address: joaquim.cabral@tecnico.ulisboa.pt.
authors.forename: Joaquim M S
authors.initials: JM
authors.lastname: Cabral
mesh_terms: D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells; D051379:Mice
keywords: Bioreactors; Cell manufacturing; Ex vivo expansion; Mesenchymal stem/stromal cells; Microcarriers; Serum/xenogeneic-free