Evidence map›Paper›PMID 40745666›Full record

ArticleStem cell research & therapy2025

Geometrical constraints dictate assembly and phenotype of human iPSC-derived motoneuronal spheroids.

Eleonora Mello, Stefano Sorrentino, Alessio Bucciarelli, Ermanno Cordelli, Elisa De Luca, Haakon Nygaard, Stefan Wendt, Alberto Rainer, Giuseppe Gigli, Lorenzo Moroni and 2 more

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Eleonora MelloInstitute of Nanotechnology (NANOTEC), National Research Council, c/o Campus EcoTekne, via Monteroni, 73100, Lecce, Italy.
Stefano SorrentinoInstitute of Nanotechnology (NANOTEC), National Research Council, c/o Campus EcoTekne, via Monteroni, 73100, Lecce, Italy.
Alessio BucciarelliBIOtech Research Center, European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Trento, Via Delle Regole 101, 38123, Trento, Italy.
Ermanno CordelliInstitute of Nanotechnology (NANOTEC), National Research Council, c/o Campus EcoTekne, via Monteroni, 73100, Lecce, Italy.
Elisa De LucaInstitute of Nanotechnology (NANOTEC), National Research Council, c/o Campus EcoTekne, via Monteroni, 73100, Lecce, Italy.
Haakon NygaardDivision of Neurology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, V6T 1Z3, Canada.
Stefan WendtDepartment of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, V6T 1Z3, Canada.
Alberto RainerDepartment of Engineering, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo 21, 00128, Rome, Italy.
Giuseppe GigliInstitute of Nanotechnology (NANOTEC), National Research Council, c/o Campus EcoTekne, via Monteroni, 73100, Lecce, Italy.
Lorenzo MoroniDepartment of Complex Tissue Regeneration, MERLN Institute for Technology- Inspired Regenerative Medicine, Maastricht University, Universiteitsingel 40, Maastricht, 6229ER, The Netherlands.
Alessandro PoliniInstitute of Nanotechnology (NANOTEC), National Research Council, c/o Campus EcoTekne, via Monteroni, 73100, Lecce, Italy.
Pamela MozeticInstitute of Nanotechnology (NANOTEC), National Research Council, c/o Campus EcoTekne, via Monteroni, 73100, Lecce, Italy. pamela.mozetic@nanotec.cnr.it.

Funding

European Union - Next Generation EU- NRRP M4.C2- Investment 1.4 "National Center for Gene Therapy and Drug based on RNA Technology" (CN00000041 CN3 RNA)Ministero della Salute Operational Health Plan, Trajectory 4, ID T4-AN-09 (CAL.HUB.RIA)Ministero della Salute "Polo High Tech Lecce" Health Operational Plan - Development and Cohesion Fund 2014-2020, Trajectory 4 (grant nr. T4-AN-01, OS2, CUP: F83C22001560003).Ministero dell'Università e della Ricerca PNC0000007-"Fit4MedRob - Fit for Medical Robotics" GrantRegione Puglia Tecnopolo per la medicina di precisione" CUP: B84I18000540002 (TecnoMed Puglia)-
6 · The paper itself

Abstract

backgroundNeuronal spheroids represent an easy and versatile solution to model neuronal tissue in vitro. Conventional approaches to generate spheroids lack accurate size control, scalability, and customizability. This is even more exacerbated in case of pluripotent stem cell (PSC) derived spheroids, which remain challenging to standardize. Microwell devices address these limitations, providing an optimal balance between accessibility and scalability. With the aim of optimizing culture conditions, we parametrically investigated the role of microwell geometry on the formation and maturation of iPSC-derived motor neuron precursor (MNP) spheroids.

methodsWe developed a customizable mold device using Digital Light Processing (DLP) 3D printing to fabricate agarose microwell arrays with distinct aspect ratios for culturing hiPSC-derived MNP spheroids with high reproducibility. We generated nine different pyramidal microwell array geometries for culturing size-controlled spheroids in the 40-140 μm diameter range. We then evaluated the differential expression of genes related to cell proliferation and motor-neuron differentiation as function of microwell geometry and spheroid size.

resultsOur results indicate that spheroid size is significantly influenced by the microwell geometry, reliably due to cell partitioning at the seeding stage. Expression of proliferation and differentiation markers, such as motor neuron and pancreas homeobox 1 (MNX1) and Islet-1 (ISL1) transcription factors, is also dependent on microwell geometry and spheroid morphological descriptors.

conclusionOur approach enables the scalable production of size-controlled MNP spheroids and underscores the effect of geometrical confinement on regulating motor neuron differentiation.

Indexed as

Induced Pluripotent Stem CellsMotor NeuronsSpheroids, CellularCell Culture TechniquesCell DifferentiationCell ProliferationHumansPhenotypePrinting, Three-DimensionalHiPSCsISL1MicrowellMNX1Motor neuronsNeuronal spheroids

Identifiers

PMID40745666
PMCPMC12315449

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.