Evidence map›Paper›PMID 23925524›Full record

ArticleIntegrative biology : quantitative biosciences from nano to macro2013

On being the right size: scaling effects in designing a human-on-a-chip.

Christopher Moraes, Joseph M Labuz, Brendan M Leung, Mayumi Inoue, Tae-Hwa Chun, Shuichi Takayama

Abstract read
In one paragraph

Article in Integrative biology : quantitative biosciences from nano to macro, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

67 citing papers in PubMed, 133 citations in OpenAlex.

  1. Passage-Dependent Size Distributions of Human-Derived Cells: Implications for Metabolic Assays.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  2. Article
  3. Article
  4. Tissue chips as headway model and incitement technology.Synthetic and systems biotechnology · 2025
    Review
  5. Targeted Cancer Therapy-on-A-Chip.Advanced healthcare materials · 2024
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. 2021 update on thyroid-associated ophthalmopathy.Journal of endocrinological investigation · 2022
    Review
  13. Scaling of joint mass and metabolism fluctuations in in silico cell-laden spheroids.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  14. Review
  15. Microphysiological systems: What it takes for community adoption.Experimental biology and medicine (Maywood, N.J.) · 2021
    Review
  16. Towards an Insulin Resistant Adipose Model on a Chip.Cellular and molecular bioengineering · 2021
    Article
  17. Review
  18. Review
  19. Article
  20. Microphysiological Systems: Design, Fabrication, and Applications.ACS biomaterials science & engineering · 2020
    Article

7 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

6 authors at 2 institutions in 2 countries.

Christopher MoraesDepartment of Biomedical Engineering, College of Engineering, University of Michigan, 2200 Bonisteel Blvd, Ann Arbor, MI 48109, USA.
Joseph M Labuz
Brendan M Leung
Mayumi Inoue
Tae-Hwa Chun
Shuichi Takayama
University of Michigan–Ann Arbor · USMichigan Medicine · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Tissue Engineering and RegenerationT32DE007057 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID H. KOHN · 1985 to 2026
$17.3M
Microfluidics in Biomedical Sciences Training ProgramT32EB005582 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FAN, XUDONG · 2005 to 2020
$3.9M
MMP14-dependent regulation of adipose tissue remodeling and function (R01)R01DK095137 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHUN, TAEHWA · 2012 to 2016
$1.7M
Modeling Therapy of Disseminated Cancer Cells in Bone Marrow (PQ 17)R01CA170198 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUKER, GARY D, TAKAYAMA, SHUICHI · 2012 to 2015
$1.4M
Microfluidic Analysis of Oscillatory Signaling Pathways Using Phase LockingR01GM096040 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TAKAYAMA, SHUICHI · 2011 to 2014
$1.1M
Role of Adipose MMP14 in Balancing Adiposity and AtherosclerosisR21HL106332 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHUN, TAEHWA · 2012 to 2013
$418k
MMP14-Dependent Regulation of Visceral Adiposity and InflammationR03DK091433 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHUN, TAEHWA · 2011 to 2012
$155k
NCI NIH HHS CA170198NCI NIH HHS R01 CA170198NHLBI NIH HHS R21 HL106332NIBIB NIH HHS T32 EB005582NIBIB NIH HHS T32 EB005582-05NIDCR NIH HHS T32 DE007057NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK095137NIDDK NIH HHS R01-DK095137NIDDK NIH HHS R03 DK091433NIGMS NIH HHS GM096040NIGMS NIH HHS R01 GM096040
6 · The paper itself

Abstract

Developing a human-on-a-chip by connecting multiple model organ systems would provide an intermediate screen for therapeutic efficacy and toxic side effects of drugs prior to conducting expensive clinical trials. However, correctly designing individual organs and scaling them relative to each other to make a functional microscale human analog is challenging, and a generalized approach has yet to be identified. In this work, we demonstrate the importance of rational design of both the individual organ and its relationship with other organs, using a simple two-compartment system simulating insulin-dependent glucose uptake in adipose tissues. We demonstrate that inter-organ scaling laws depend on both the number of cells and the spatial arrangement of those cells within the microfabricated construct. We then propose a simple and novel inter-organ 'metabolically supported functional scaling' approach predicated on maintaining in vivo cellular basal metabolic rates by limiting resources available to cells on the chip. This approach leverages findings from allometric scaling models in mammals that limited resources in vivo prompt cells to behave differently than in resource-rich in vitro cultures. Although applying scaling laws directly to tissues can result in systems that would be quite challenging to implement, engineering workarounds may be used to circumvent these scaling issues. Specific workarounds discussed include the limited oxygen carrying capacity of cell culture media when used as a blood substitute and the ability to engineer non-physiological structures to augment organ function, to create the transport-accessible, yet resource-limited environment necessary for cells to mimic in vivo functionality. Furthermore, designing the structure of individual tissues in each organ compartment may be a useful strategy to bypass scaling concerns at the inter-organ level.

Indexed as

Adipose TissueBasal MetabolismBiomimeticsComputer SimulationGlucoseHumansTissue EngineeringGlucose

Identifiers

PMID23925524
PMCPMC3787867
OpenAlexW2038998535

What OpenQuestion holds

Textmetadata
LicenceTDM
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.