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Biotechnol Bioeng. 2018 Aug;115(8):2061-2066. doi: 10.1002/bit.26719. Epub 2018 May 1.

Chemically controlled aggregation of pluripotent stem cells.

Lipsitz YY1, Tonge PD1,2, Zandstra PW1,2,3,4,5,6.

Author information

1
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
2
Centre for Commercialization of Regenerative Medicine, Toronto, Ontario, Canada.
3
The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
4
Medicine by Design: A Canada First Research Excellence Fund Program, University of Toronto, Toronto, Ontario, Canada.
5
School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada.
6
Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

Heterogeneity in pluripotent stem cell (PSC) aggregation leads to variability in mass transfer and signaling gradients between aggregates, which results in heterogeneous differentiation and therefore variability in product quality and yield. We have characterized a chemical-based method to control aggregate size within a specific, tunable range with low heterogeneity, thereby reducing process variability in PSC expansion. This method enables controlled, scalable, stirred suspension-based manufacturing of PSC cultures that are critical for the translation of regenerative medicine strategies to clinical products.

KEYWORDS:

aggregation; bioreactor: pluripotent stem cell (PSC); process variability; stem cells

PMID:
29679475
PMCID:
PMC6055717
DOI:
10.1002/bit.26719
[Indexed for MEDLINE]
Free PMC Article

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