Evidence map›Paper›PMID 28459451›Full record

ArticleNature biotechnology2017

Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells.

Karl R Koehler, Jing Nie, Emma Longworth-Mills, Xiao-Ping Liu, Jiyoon Lee, Jeffrey R Holt, Eri Hashino

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
212citing papers in PubMed, 1 pooled it
14.3field-weighted citation impact, top 1% of its field
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

212 citing papers in PubMed, 1 synthesis or guideline pooled it, 325 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Inner Ear Organoids: Recent Progress and Challenges.Stem cell reviews and reports · 2026
    Review
  4. Article
  5. Review
  6. Functionalized Biomimetic Scaffolds for Human-Derived Auditory Neural Circuit Construction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  7. Review
  8. Article
  9. Recent Progress in Mechanism-Based Therapies forInternational journal of molecular sciences · 2026
    Review
  10. Stem cell-based and gene editing strategies in the treatment of congenital and acquired sensorineural hearing loss: a narrative review.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
    Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. AAV-mediated exon skipping therapy for Usher syndrome, type 2A.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  18. Review
  19. Review
  20. Review

152 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Karl R KoehlerDepartment of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jing NieDepartment of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Emma Longworth-MillsDepartment of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Xiao-Ping LiuDepartments of Otolaryngology and Neurology, F.M. Kirby Neurobiology Center Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
Jiyoon LeeDepartment of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jeffrey R HoltDepartments of Otolaryngology and Neurology, F.M. Kirby Neurobiology Center Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
Eri HashinoDepartment of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Indiana University – Purdue University Indianapolis · USBoston Children's Hospital · USIndiana University School of Medicine

Funding

Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
Modeling Inner Ear Differentiation with Pluripotent Stem CellsR01DC013294 · NIDCD · INDIANA UNIVERSITY INDIANAPOLIS · PI Eri Hashino · 2014 to 2026
$7.1M
Mouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SAHIN, MUSTAFA · 2016 to 2020
$5.2M
EXTRAMURAL RESEARCH FACILITIES IMPROVEMENT: NEUROLOGICAL DISORDERS:ALZ, PDC06RR020128 · NCRR · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI FIFE, ROSE S · 2004 to 2004
$3.7M
Generation of human skin organoids from pluripotency (Admin Supplement)R01AR075018 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI Karl Russell Koehler · 2019 to 2026
$3.6M
Modeling Otic Neurogenesis in Human Stem Cell-Derived OrganoidsR03DC015624 · NIDCD · INDIANA UNIVERSITY INDIANAPOLIS · PI KOEHLER, KARL RUSSELL · 2016 to 2018
$471k
Sonic Hedgehog Signaling in Inner Ear Organoid DevelopmentF31DC015968 · NIDCD · INDIANA UNIVERSITY INDIANAPOLIS · PI LONGWORTH-MILLS, EMMA · 2016 to 2018
$89k
NCATS NIH HHS UL1 TR001108NCRR NIH HHS C06 RR020128NIAMS NIH HHS R01 AR075018NICHD NIH HHS U54 HD090255NIDCD NIH HHS F31 DC015968NIDCD NIH HHS R01 DC013294NIDCD NIH HHS R03 DC015624
6 · The paper itself

Abstract

The derivation of human inner ear tissue from pluripotent stem cells would enable in vitro screening of drug candidates for the treatment of hearing and balance dysfunction and may provide a source of cells for cell-based therapies of the inner ear. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and WNT signaling to generate multiple otic-vesicle-like structures from a single stem-cell aggregate. Over 2 months, the vesicles develop into inner ear organoids with sensory epithelia that are innervated by sensory neurons. Additionally, using CRISPR-Cas9, we generate an ATOH1-2A-eGFP cell line to detect hair cell induction and demonstrate that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells. Our culture system should facilitate the study of human inner ear development and research on therapies for diseases of the inner ear.

Indexed as

Cells, CulturedEar, InnerHair Cells, Auditory, InnerHumansOrganogenesisOrganoidsPluripotent Stem CellsTissue Engineering

Identifiers

PMID28459451
PMCPMC5462862
OpenAlexW2610506730

What OpenQuestion holds

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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.