Evidence map›Paper›PMID 39243942›Full record

ArticleJournal of advanced research2025

Brain organoid maturation and implantation integration based on electrical signals input.

Xiao-Hong Li, Nan Hu, Zhe-Han Chang, Jian-Xin Shi, Xiu Fan, Meng-Meng Chen, Shuang-Qing Bao, Chong Chen, Jia-Chen Zuo, Xiao-Wang Zhang and 2 more

Abstract read
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
–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

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  14. Opportunities and Challenges of Brain-on-a-Chip Interfaces.Cyborg and bionic systems (Washington, D.C.) · 2025
    Review
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  16. Novel advanced patient-derivedFrontiers in neurology
    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.

Xiao-Hong LiAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China. Electronic address: xhli18@tju.edu.cn.
Nan HuAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Zhe-Han ChangAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Jian-Xin ShiAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Xiu FanAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Meng-Meng ChenAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Shuang-Qing BaoAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Chong ChenAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Jia-Chen ZuoAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Xiao-Wang ZhangAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Jing-Jing WangAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
Dong MingAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China. Electronic address: richardming@tju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionBrain organoids are believed to be able to regenerate impaired neural circuits and reinstate brain functionality. The neuronal activity of organoids is considered a crucial factor for restoring host function after implantation. However, the optimal stage of brain organoid post-transplantation has not yet been established. External electrical signal plays a crucial role in the physiology and development of a majority of human tissues. However, whether electrical input modulates the development of brain organoids, making them ideal transplant donors, is elusive.

methodsBioelectricity was input into cortical organoids by electrical stimulation (ES) with a multi-electrode array (MEA) to obtain a better-transplanted candidate with better viability and maturity, realizing structural-functional integration with the host brain.

resultsWe found that electrical stimulation facilitated the differentiation and maturation of organoids, displaying well-defined cortical plates and robust functional electrophysiology, which was probably mediated via the pathway of calcium-calmodulin (CaM) dependent protein kinase II (CAMK II)-protein kinase A (PKA)-cyclic-AMP response binding protein (pCREB). The ES-pretreated D40 organoids displayed superior cell viability and higher cell maturity, and were selected to transplant into the damaged primary sensory cortex (S1) of host. The enhanced maturation was exhibited within grafts after transplantation, including synapses and complex functional activities. Moreover, structural-functional integration between grafts and host was observed, conducive to strengthening functional connectivity and restoring the function of the host injury.

conclusionOur findings supported that electrical stimulation could promote the development of cortical organoids. ES-pretreated organoids were better-transplanted donors for strengthening connectivity between grafts and host. Our work presented a new physical approach to regulating organoids, potentially providing a novel translational strategy for functional recovery after brain injury. In the future, the development of 3D flexible electrodes is anticipated to overcome the drawbacks of 2D planar MEA, promisingly achieving multimodal stimulation and long-term recordings of brain organoids.

Indexed as

BrainOrganoidsAnimalsCell DifferentiationElectric StimulationHumansMiceNeuronsBrain injuryCortical organoidsDonorElectrical stimulationMaturationTransplantation

Identifiers

PMID39243942
PMCPMC12225903

What OpenQuestion holds

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Registered trials

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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.