Evidence map›Paper›PMID 35044538›Full record

ArticleCellular and molecular life sciences : CMLS2022

Bioengineered models of Parkinson's disease using patient-derived dopaminergic neurons exhibit distinct biological profiles in a 3D microenvironment.

Nicholas J Fiore, Yosif M Ganat, Kapil Devkota, Rebecca Batorsky, Ming Lei, Kyongbum Lee, Lenore J Cowen, Gist Croft, Scott A Noggle, Thomas J F Nieland and 1 more

Open access · greenAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Engineering Silk Fibroin-Based Biomaterials for Neural Repair.Advanced materials (Deerfield Beach, Fla.) · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. The Evolution of Technology-Driven In Vitro Models for Neurodegenerative Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  10. A Hierarchical Mechanotransduction System: From Macro to Micro.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  11. Review
  12. Article
  13. 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

11 authors at 2 institutions in 1 country.

Nicholas J FioreDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.
Yosif M GanatThe New York Stem Cell Foundation Research Institute, New York, NY, USA.
Kapil DevkotaDepartment of Computer Science, Tufts University, Medford, MA, USA.
Rebecca BatorskyResearch Technology, Tufts University, Medford, MA, USA.
Ming LeiDepartment of Chemical and Biological Engineering, Tufts University, Medford, MA, USA.
Kyongbum LeeDepartment of Chemical and Biological Engineering, Tufts University, Medford, MA, USA.
Lenore J CowenDepartment of Computer Science, Tufts University, Medford, MA, USA.
Gist CroftThe New York Stem Cell Foundation Research Institute, New York, NY, USA.
Scott A NoggleThe New York Stem Cell Foundation Research Institute, New York, NY, USA.
Thomas J F NielandDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA. thomas.nieland@tufts.edu.
David L KaplanDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA. david.kaplan@tufts.edu.ORCID http://orcid.org/0000-0002-9245-7774
Tufts University · USNew York Stem Cell Foundation · US

Funding

Tissue Engineering Resource Center: TTDP41EB027062 · NIBIB · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Gordana Vunjak-Novakovic · 2019 to 2026
$12.6M
Acquisition of Leica confocal/multiphoton microscopeS10OD021624 · OD · TUFTS UNIVERSITY MEDFORD · PI GEORGAKOUDI, IRENE · 2016 to 2016
$600k
National Science Foundation 1337760National Science Foundation 1934553NIBIB NIH HHS P41 EB027062NIH HHS P41EB027062NIH HHS S10 OD021624
6 · The paper itself

Abstract

Three-dimensional (3D) in vitro culture systems using human induced pluripotent stem cells (hiPSCs) are useful tools to model neurodegenerative disease biology in physiologically relevant microenvironments. Though many successful biomaterials-based 3D model systems have been established for other neurogenerative diseases, such as Alzheimer's disease, relatively few exist for Parkinson's disease (PD) research. We employed tissue engineering approaches to construct a 3D silk scaffold-based platform for the culture of hiPSC-dopaminergic (DA) neurons derived from healthy individuals and PD patients harboring LRRK2 G2019S or GBA N370S mutations. We then compared results from protein, gene expression, and metabolic analyses obtained from two-dimensional (2D) and 3D culture systems. The 3D platform enabled the formation of dense dopamine neuronal network architectures and developed biological profiles both similar and distinct from 2D culture systems in healthy and PD disease lines. PD cultures developed in 3D platforms showed elevated levels of α-synuclein and alterations in purine metabolite profiles. Furthermore, computational network analysis of transcriptomic networks nominated several novel molecular interactions occurring in neurons from patients with mutations in LRRK2 and GBA. We conclude that the brain-like 3D system presented here is a realistic platform to interrogate molecular mechanisms underlying PD biology.

Indexed as

BioengineeringCell Culture Techniques, Three DimensionalCells, CulturedDopaminergic NeuronsHumansInduced Pluripotent Stem CellsNeurogenesisParkinson DiseaseSilkTissue ScaffoldsSilk3D bioengineered disease modelDopaminergic neuronsLink prediction analysisMetabolomicsNetwork biologyTranscriptomics

Identifiers

PMID35044538
PMCPMC8908880
OpenAlexW4205181071

What Socratic 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 Socratic graph.