Stirred tank bioreactor culture combined with serum-/xenogeneic-free culture medium enables an efficient expansion of umbilical cord-derived mesenchymal stem/stromal cells

Autor(es)

Mizukami, Amanda ; Fernandes-Platzgummer, Ana ; Carmelo, Joana G. ; Swiech, Kamilla ; Covas, Dimas T. ; Cabral, Joaquim M. S. ; da Silva, Claudia L.

• Tipo de documento: Artigo Científico
• Fonte: Biotechnology Journal; v. 11, n. 8, p. 1048-1059, AUG 2016.
• Citações Web of Science: 12

Resumo

Mesenchymal stem/stromal cells (MSC) are being widely explored as promising candidates for cell-based therapies. Among the different human MSC origins exploited, umbilical cord represents an attractive and readily available source of MSC that involves a non-invasive collection procedure. In order to achieve relevant cell numbers of human MSC for clinical applications, it is crucial to develop scalable culture systems that allow bioprocess control and monitoring, combined with the use of serum/xenogeneic (xeno)-free culture media. In the present study, we firstly established a spinner flask culture system combining gelatin-based Cultispher((R))S microcarriers and xeno-free culture medium for the expansion of umbilical cord matrix (UCM)-derived MSC. This system enabled the production of 2.4 (+/- 1.1) x10(5) cells/mL (n = 4) after 5 days of culture, corresponding to a 5.3 (+/- 1.6)-fold increase in cell number. The established protocol was then implemented in a stirred-tank bioreactor (800 mL working volume) (n = 3) yielding 115 million cells after 4 days. Upon expansion under stirred conditions, cells retained their differentiation ability and immunomodulatory potential. The development of a scalable microcarrier-based stirred culture system, using xeno-free culture medium that suits the intrinsic features of UCM-derived MSC represents an important step towards a GMP compliant large-scale production platform for these promising cell therapy candidates. (AU)

• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 12/23228-4 - Expansão in vitro de células estromais mesenquimais e caracterização do secretoma: aplicações terapêuticas e biotecnológicas
• Beneficiário: Amanda Mizukami Martins
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/23599-5 - Expansão de células estromais humanas derivadas da matriz do cordão umbilical em biorreatores em condições livres de soro e xenoantígenos
• Beneficiário: Amanda Mizukami Martins
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado