A Fully-Closed and Automated Hollow Fiber Bioreactor for Clinical-Grade Manufacturing of Human Mesenchymal Stem/Stromal Cells
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The use of mesenchymal stem/stromal cells (MSC) for cellular therapy and regenerative medicine has been boosted by the increasing demand for biological substitutes that can restore, maintain and/or improve the functions of damaged tissues and organs in several diseases. The successful clinical implementation of MSC-based therapies must address the need for ex-vivo expansion due to the low frequency of these cells in the available tissues and the high doses (1-100 × 106cells/kg patient) required for an infusion. The manufacturing of high cell doses/lot will be possible through the use of bioreactors that present several advantages when compared to the traditional flask-based methods: traceability, scalability, reduced manual handling and easy monitorability and control of culture parameters. Moreover, the use of defined serum-/xenogeneic(xeno)-free culture medium formulations could result in substantial improvements for MSC production in terms of cell reproducibility, stability and...
This work was supported by FAPESP (2012/23228-4), CTC- Center for Cell-based Therapies (FAPESP 2013/08135-2) and National Institute of Science and Technology in Stem Cell and Cell Therapy (CNPq 573754-2008-0 and FAPESP 2008/578773). The authors acknowledge Fundação para a Ciência e a Tecnologia (FCT), Portugal, through iBB – Institute for Bioengineering and Biosciences under the project UID/BIO/04565/ 2013 and Programa Operacional Regional de Lisboa 2020 (project no. 007317) and grant SFRH/BD/90081/2012 (awarded to FM). We also acknowledge the funding received from Programa Operacional Regional de Lisboa 2020 through the project PRECISE - Accelerating progress toward the new era of precision medicine (Project N. 16394).
Compliance with Ethical Standards
All procedures performed with human samples were in accordance with the ethical standards of the institutional and/or national research committee.
Informed consent was obtained from all individual participants included in the study.
Disclosure of Potential Conflict of Interest
The authors have declared that there is no conflict of interest.
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