Evidence map›Paper›PMID 36314397›Full record

ArticleAdvanced healthcare materials2022

Large-Scale Production of Wholly Cellular Bioinks via the Optimization of Human Induced Pluripotent Stem Cell Aggregate Culture in Automated Bioreactors.

Debbie L L Ho, Stacey Lee, Jianyi Du, Jonathan D Weiss, Tony Tam, Soham Sinha, Danielle Klinger, Sean Devine, Art Hamfeldt, Hope T Leng and 12 more

Abstract read
In one paragraph

Article in Advanced healthcare materials, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. 3D Bioprinting Functional Engineered Heart Tissues.International journal of molecular sciences · 2025
    Review
  10. 3D printing functional liver discoids.Annals of translational medicine · 2025
    Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. A review of 3D bioprinting for organoids.Medical review (2021) · 2025
    Review
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Debbie L L HoDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0001-9799-4838
Stacey LeeDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0001-5645-8449
Jianyi DuDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0001-9838-6308
Jonathan D WeissDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0002-1033-9206
Tony TamDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0002-0288-5434
Soham SinhaDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0001-8598-0543
Danielle KlingerDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0002-5379-7979
Sean DevineSartorius Stedim North America Inc, 565 Johnson Avenue, Bohemia, NY, 11716, USA.
Art HamfeldtSartorius Stedim North America Inc, 565 Johnson Avenue, Bohemia, NY, 11716, USA.
Hope T LengDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0001-5097-854X
Jessica E HerrmannDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0002-3357-8437
Mengdi HeMaterials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0002-3841-9574
Lee G FradkinDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0002-5282-2984
Tze Kai TanInstitute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID 0000-0002-7359-5303
David StandishSartorius Stedim North America Inc, 565 Johnson Avenue, Bohemia, NY, 11716, USA.
Peter TomaselloSartorius Stedim North America Inc, 565 Johnson Avenue, Bohemia, NY, 11716, USA.
Donald TraulSartorius Stedim North America Inc, 565 Johnson Avenue, Bohemia, NY, 11716, USA.
Noushin DianatSartorius Stedim France S.A.S, Zone Industrielle les Paluds, Avenue de Jouques CS 71058, Aubagne Cedex, 13781, France.
Rukmini LadiSartorius Stedim North America Inc, 565 Johnson Avenue, Bohemia, NY, 11716, USA.
Quentin VicardSartorius Stedim France S.A.S, Zone Industrielle les Paluds, Avenue de Jouques CS 71058, Aubagne Cedex, 13781, France.
Kishore KatikireddySartorius Stedim North America Inc, 565 Johnson Avenue, Bohemia, NY, 11716, USA.ORCID 0000-0002-6655-5370
Mark A Skylar-ScottDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.ORCID 0000-0003-3496-7124

Funding

Hatching Organoids for Continuous Tissue Production PipelinesR21EB033051 · NIBIB · STANFORD UNIVERSITY · PI SKYLAR-SCOTT, MARK A. · 2022 to 2023
$630k
Nikon A1Rsi resonant spectral confocal microscopeS10OD010580 · OD · STANFORD UNIVERSITY · PI FULLER, MARGARET T · 2013 to 2013
$377k
NCRR NIH HHS 1S10OD010580NIBIB NIH HHS R21 EB033051NIH HHS R21EB033051NIH HHS S10 OD010580
6 · The paper itself

Abstract

Combining the sustainable culture of billions of human cells and the bioprinting of wholly cellular bioinks offers a pathway toward organ-scale tissue engineering. Traditional 2D culture methods are not inherently scalable due to cost, space, and handling constraints. Here, the suspension culture of human induced pluripotent stem cell-derived aggregates (hAs) is optimized using an automated 250 mL stirred tank bioreactor system. Cell yield, aggregate morphology, and pluripotency marker expression are maintained over three serial passages in two distinct cell lines. Furthermore, it is demonstrated that the same optimized parameters can be scaled to an automated 1 L stirred tank bioreactor system. This 4-day culture results in a 16.6- to 20.4-fold expansion of cells, generating approximately 4 billion cells per vessel, while maintaining >94% expression of pluripotency markers. The pluripotent aggregates can be subsequently differentiated into derivatives of the three germ layers, including cardiac aggregates, and vascular, cortical and intestinal organoids. Finally, the aggregates are compacted into a wholly cellular bioink for rheological characterization and 3D bioprinting. The printed hAs are subsequently differentiated into neuronal and vascular tissue. This work demonstrates an optimized suspension culture-to-3D bioprinting pipeline that enables a sustainable approach to billion cell-scale organ engineering.

Indexed as

Induced Pluripotent Stem CellsBioreactorsCell Culture TechniquesCell LineCell ProliferationHumans3D bioprintingcell manufacturingorganoidspluripotent stem cellssuspension culture

Identifiers

PMID36314397
PMCPMC10234214

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.