Cited by 265Pluripotent Stem Cells ResearchFluid Dynamics and MixingMesenchymal stem cell research

Scalable Stirred-Suspension Bioreactor Culture of Human Pluripotent Stem Cells

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Kehoe, Daniel E., Jing, Donghui, Lock, Lye T., Tzanakakis, Emmanuel S.·2010·Tissue Engineering Part A

Abstract

Advances in stem cell biology have afforded promising results for the generation of various cell types for therapies against devastating diseases. However, a prerequisite for realizing the therapeutic potential of stem cells is the development of bioprocesses for the production of stem cell progeny in quantities that satisfy clinical demands. Recent reports on the expansion and directed differentiation of human embryonic stem cells (hESCs) in scalable stirred-suspension bioreactors (SSBs) demonstrated that large-scale production of therapeutically useful hESC progeny is feasible with current state-of-the-art culture technologies. Stem cells have been cultured in SSBs as aggregates, in microcarrier suspension and after encapsulation. The various modes in which SSBs can be employed for the cultivation of hESCs and human induced pluripotent stem cells (hiPSCs) are described. To that end, this is the first account of hiPSC cultivation in a microcarrier stirred-suspension system. Given that cultured stem cells and their differentiated progeny are the actual products used in tissue engineering and cell therapies, the impact of bioreactor's operating conditions on stem cell self-renewal and commitment should be considered. The effects of variables specific to SSB operation on stem cell physiology are discussed. Finally, major challenges are presented which remain to be addressed before the mainstream use of SSBs for the large-scale culture of hESCs and hiPSCs.

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Crossref · 10.1089/ten.tea.2009.0454

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  • A fundamental challenge to scaling hPSC differentiation in suspension culture is the fluid convection necessary to keep cells from settling, which is made more difficult because hPSCs require either microcarriers or culture in aggregates.

    “A fundamental challenge to scaling hPSC differentiation in suspension culture is the fluid convection necessary to keep cells from settling, which is made more difficult due to hPSCs requiring either microcarriers or culture in aggregates.178”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [178]

    The Agitation section (page unavailable) says stirring keeps aggregates or microcarriers suspended and that shear can damage cells on them, supporting the stated scale-up challenge. But the paper also identifies encapsulation as a suspension-culture mode, so it does not support the categorical claim that hPSCs require either microcarriers or aggregates. (LLM, conf=0.85)

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3 of the 179 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. [1]1. Palsson, B.O., and Bhatia, S.N. Tissue Engineering. Upper Saddle River, NJ: Pearson Prentice Hall, 2004.
  2. [83]83. Hinze, J.O. Turbulence. New York: McGraw-Hill, 1975.

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Authors
Kehoe, D. E., Jing, D., Lock, L. T., & Tzanakakis, E. S.
Affiliations
University at Buffalo, State University of New York (US)
Corresponding author
Tzanakakis, Emmanuel S.
Venue
Tissue Engineering Part A
Published
2010-02
Volume
16
Issue
2
Pages
405-421
ISSN
  • 1937-3341 (ISSN-L)
  • 1937-335X
OpenAlex
W1983810137
Cited by
264
References
179
Citations by year
2026: 3 · 2025: 5 · 2024: 11 · 2023: 14 · 2022: 3 · 2021: 17 · 2020: 9 · 2019: 10 · 2018: 17 · 2017: 16 · 2016: 19 · 2015: 18 · 2014: 27 · 2013: 33 · 2012: 27
FWCI
1.56
Type
journal article
Language
en
Open access
Locations
  • Tissue Engineering Part A (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Harvard University
  • Amrita Vishwa Vidyapeetham University
  • National Institutes of Health
  • Office of Science
  • Harvard Stem Cell Institute
  • National Heart, Lung, and Blood Institute (R21HL092398, HL092398)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Physical Sciences › Engineering › Biomedical Engineering › Fluid Dynamics and Mixing
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
stirred suspension bioreactors, human pluripotent stem cells, human embryonic stem cells, human induced pluripotent stem cells, large-scale cell culture, microcarrier culture, encapsulation, stem cell self-renewal, directed differentiation, bioprocess scale-up, cell therapy
MeSH terms
Cells, Cultured, Humans, Cell Culture Techniques, Bioreactors, Pluripotent Stem Cells

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