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Cytotherapy. 2019 Jan;21(1):76-82. doi: 10.1016/j.jcyt.2018.10.009. Epub 2018 Nov 27.

Closed loop bioreactor system for the ex vivo expansion of human T cells.

Author information

1
Center for Surgery, Innovation, and Bioengineering, Department of Surgery, Massachusetts General Hospital and the Shriners Hospitals for Children, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA.
2
Harvard Medical School, Boston, Massachusetts, USA; Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
3
Center for Surgery, Innovation, and Bioengineering, Department of Surgery, Massachusetts General Hospital and the Shriners Hospitals for Children, Boston, Massachusetts, USA; Harvard Stem Cell Institute, Cambridge, Massachusetts, USA; Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA. Electronic address: biju_parekkadan@hms.harvard.edu.

Abstract

BACKGROUND AIM:

Translation of therapeutic cell therapies to clinical-scale products is critical to realizing widespread success. Currently, however, there are limited tools that are accessible at the research level and readily scalable to clinical-scale needs.

METHODS:

We herein developed and assessed a closed loop bioreactor system in which (i) a highly gas-permeable silicone material was used to fabricate cell culture bags and (ii) dynamic flow was introduced to allow for dissociation of activated T-cell aggregates.

RESULTS:

Using this system, we find superior T-cell proliferation compared with conventional bag materials and flasks, especially at later time points. Furthermore, intermittent dynamic flow could easily break apart T-cell clusters.

CONCLUSIONS:

Our novel closed loop bioreactor system is amenable to enhanced T-cell proliferation and has broader implications for being easily scaled for use in larger need settings.

KEYWORDS:

T cells; biomanufacturing; bioreactors; immunotherapy

PMID:
30497956
PMCID:
PMC6333522
DOI:
10.1016/j.jcyt.2018.10.009
[Indexed for MEDLINE]
Free PMC Article

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