Evidence map›Paper›PMID 33982436›Full record

ReviewClinical and translational science2021

3D cell culture models: Drug pharmacokinetics, safety assessment, and regulatory consideration.

Hongbing Wang, Paul C Brown, Edwin C Y Chow, Lorna Ewart, Stephen S Ferguson, Suzanne Fitzpatrick, Benjamin S Freedman, Grace L Guo, William Hedrich, Scott Heyward and 11 more

Open access · goldAbstract readReview
In one paragraph

Review in Clinical and translational science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed, 2 pooled it
11.5field-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

118 citing papers in PubMed, 2 syntheses or guidelines pooled it, 196 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Biomimetic Scaffold-Based 3D Models for Decoding Cancer Biology and Advancing Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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58 more citing papers are in PubMed but not listed here.

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

21 authors at 13 institutions in 2 countries.

Hongbing WangDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.
Paul C BrownCenter for Drug Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Edwin C Y ChowOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Lorna EwartEmulate, Boston, Massachusetts, USA.
Stephen S FergusonDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Suzanne FitzpatrickOffice of the Center Director, Center for Food Safety and Applied Nutrition, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Benjamin S FreedmanDivision of Nephrology, Department of Pathology, Kidney Research Institute, and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, USA.
Grace L GuoDepartment of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.
William HedrichPharmaceutical Candidate Optimization, Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Princeton, New Jersey, USA.
Scott HeywardBioIVT, Halethorpe, Maryland, USA.
James HickmanNanoScience Technology Center, University of Central Florida, Orlando, Florida, USA.
Nina IsoherranenDepartment of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, USA.
Albert P LiIn Vitro ADMET Laboratories, Columbia, Maryland, USA.
Qi LiuOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Shannon M MumenthalerLawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, California, USA.
James PolliDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.
William R ProctorPredictive Toxicology, Safety Assessment, Genentech, Inc, South San Francisco, California, USA.
Alexandre RibeiroOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Jian-Ying WangDepartment of Surgery, Cell Biology Group, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Ronald L WangeCenter for Drug Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Shiew-Mei HuangOffice of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Center for Drug Evaluation and Research · USUnited States Food and Drug Administration · USUniversity of Maryland, Baltimore · USUniversity of Washington · USBristol-Myers Squibb (United States) · USCenter for Food Safety and Applied Nutrition · USEmulate (United States) · USIn Vitro Admet Laboratories (United States) · USNational Institute of Environmental Health Sciences · USPredictive Science (United States) · USRutgers, The State University of New Jersey · USUniversity of Central Florida · USUniversity of Southern California · US

Funding

Intestinal Mucosal Growth in Health & Surgical DiseasesR01DK057819 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI Jian-Ying Wang · 2000 to 2026
$7.4M
Surgical Studies of Gut PermeabilityR01DK068491 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI Jian-Ying Wang · 2004 to 2026
$7.0M
Mucosal Repair in Gut Surgical DisordersR01DK061972 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI WANG, JIAN-YING · 2002 to 2023
$6.7M
Tissue Chip Data to the Microphysiology Systems Database (MPS-Db) Supplement to A Microphysiological System for Kidney Disease Modeling and Drug Efficacy TestingUH3TR002158 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2019 to 2021
$4.2M
Cell specific delivery of novel therapies to enhance glomerular regeneration and repairUC2DK126006 · NIDDK · UNIVERSITY OF WASHINGTON · PI SHANKLAND, STUART JAMES · 2020 to 2024
$4.0M
A Microphysiological System for Kidney Disease Modeling and Drug Efficacy TestingUG3TR002158 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2017 to 2018
$2.9M
Safety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological SystemsUH3TR003288 · NCATS · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON, HIMMELFARB, JONATHAN · 2022 to 2024
$2.3M
A microengineered colon cancer-chip designed to investigate tumor-stromal interactions driving cancer progressionR01CA241137 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MUMENTHALER, SHANNON MICHELLE · 2021 to 2025
$2.3M
SCGE Comparative Studies SupplementU01DK127553 · NIDDK · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON · 2020 to 2022
$2.2M
A Human Organoid Model of Polycystic Kidney DiseaseR01DK117914 · NIDDK · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON · 2018 to 2022
$1.8M
Safety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological SystemsUG3TR003288 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN, KRETZLER, MATTHIAS · 2020 to 2021
$1.7M
Improving the Safety of Genome Editing With Human Kidney OrganoidsU01EB028892 · NIBIB · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON · 2019 to 2019
$713k
BLRD VA I01 BX000332BLRD VA IK6 BX004213NCATS NIH HHS UG3 TR002158NCATS NIH HHS UG3 TR003288NCATS NIH HHS UH3 TR002158NCATS NIH HHS UH3 TR003288NCI NIH HHS R01 CA241137NIBIB NIH HHS U01 EB028892NIDDK NIH HHS R01 DK057819NIDDK NIH HHS R01 DK061972NIDDK NIH HHS R01 DK068491NIDDK NIH HHS R01 DK117914NIDDK NIH HHS U01 DK127553NIDDK NIH HHS UC2 DK126006
6 · The paper itself

Abstract

Nonclinical testing has served as a foundation for evaluating potential risks and effectiveness of investigational new drugs in humans. However, the current two-dimensional (2D) in vitro cell culture systems cannot accurately depict and simulate the rich environment and complex processes observed in vivo, whereas animal studies present significant drawbacks with inherited species-specific differences and low throughput for increased demands. To improve the nonclinical prediction of drug safety and efficacy, researchers continue to develop novel models to evaluate and promote the use of improved cell- and organ-based assays for more accurate representation of human susceptibility to drug response. Among others, the three-dimensional (3D) cell culture models present physiologically relevant cellular microenvironment and offer great promise for assessing drug disposition and pharmacokinetics (PKs) that influence drug safety and efficacy from an early stage of drug development. Currently, there are numerous different types of 3D culture systems, from simple spheroids to more complicated organoids and organs-on-chips, and from single-cell type static 3D models to cell co-culture 3D models equipped with microfluidic flow control as well as hybrid 3D systems that combine 2D culture with biomedical microelectromechanical systems. This article reviews the current application and challenges of 3D culture systems in drug PKs, safety, and efficacy assessment, and provides a focused discussion and regulatory perspectives on the liver-, intestine-, kidney-, and neuron-based 3D cellular models.

Indexed as

Cell Culture Techniques, Three DimensionalAnimal Use AlternativesCells, CulturedCoculture TechniquesDrug Evaluation, PreclinicalHumansIntestinesKidneyLiverNeuronsSpheroids, CellularToxicity TestsUnited StatesUnited States Food and Drug Administration

Identifiers

PMID33982436
PMCPMC8504835
OpenAlexW3160762332

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.