Evidence map›Paper›PMID 42296971›Full record

ArticleCell reports methods2026

Simple 3D-printed stirred bioreactor enhances retinal organoid production via improved oxygenation.

Kyle H Schwab, Philsang Hwang, Ki Yoon Nam, Zachary Batz, Suja Hiriyanna, Florian Régent, Nicole Y Morgan, Peter I Lelkes, Tiansen Li

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PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports methods, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Organoids for disease modeling and treatment: state-of-the-art.Experimental hematology & oncology · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Kyle H SchwabNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA; Department of Bioengineering, Temple University, Philadelphia, PA, USA. Electronic address: kyle.schwab@nih.gov.
Philsang HwangOcular Gene Therapy Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Ki Yoon NamNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Zachary BatzNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Suja HiriyannaOcular Gene Therapy Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Florian RégentNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Nicole Y MorganBiomedical Engineering and Physical Science Shared Resource, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
Peter I LelkesDepartment of Bioengineering, Temple University, Philadelphia, PA, USA.
Tiansen LiNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA; Ocular Gene Therapy Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: tiansen.li@nei.nih.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Static cultures, the standard for growing monolayer cells, were presumed suitable for and widely used during the initial adherent phase of retinal organoid (RO) differentiation. This assumption may be incorrect, as monolayer human pluripotent stem cells (hPSCs) become highly structured and multilayered during neural induction. These emerging complex structures likely consume more oxygen than passive diffusion can provide. To test this hypothesis, we measured oxygen at the vessel bottom and found levels fell below 1%, indicating non-physiological hypoxia. This condition contributed to cellular necrosis and degeneration. To address this problem, we developed a 3D-printed stirred bioreactor (SBR) that maintains physiological oxygen levels. This approach significantly improved organoid yield and quality while being easily adaptable to typical laboratory workflows. We conclude that non-physiological hypoxia, a previously unappreciated condition, is a limiting factor underlying inconsistent RO yield and quality. Physiological oxygen levels can be restored by the SBR platform, resulting in greater consistency and improved outcomes.

Indexed as

BioreactorsOrganoidsOxygenPrinting, Three-DimensionalRetinaCell DifferentiationHumansInduced Pluripotent Stem CellsOxygen3D-printingbioreactorCP: stem cellhuman-induced pluripotent stem cellshypoxiamathematical modelingoxygenationretinal organoid

Identifiers

PMID42296971
PMCPMC13494550

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LicenceCC BY-NC-ND
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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.