Evidence map›Paper›PMID 40069892›Full record

ArticleStem cell research & therapy2025

Enhanced mitochondrial function and delivery from adipose-derived stem cell spheres via the EZH2-H3K27me3-PPARγ pathway for advanced therapy.

Ming-Min Chang, Dinh Toi Chu, Sheng-Che Lin, Jung-Shun Lee, Thuy Duong Vu, Hue Thi Vu, Thamil Selvee Ramasamy, Shau-Ping Lin, Chia-Ching Wu

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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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

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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

3 citing papers in PubMed.

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4 · The record

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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

9 authors.

Ming-Min ChangDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan, 70101, Taiwan.
Dinh Toi ChuFaculty of Applied Sciences, International School, Vietnam National University, Hanoi, 1000, Vietnam.
Sheng-Che LinDivision of Plastic and Reconstructive Surgery, Tainan Municipal An-Nan Hospital-China Medical University, Tainan, 70965, Taiwan.
Jung-Shun LeeDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan, 70101, Taiwan.
Thuy Duong VuFaculty of Applied Sciences, International School, Vietnam National University, Hanoi, 1000, Vietnam.
Hue Thi VuFaculty of Applied Sciences, International School, Vietnam National University, Hanoi, 1000, Vietnam.
Thamil Selvee RamasamyStem Cell Biology Laboratory, Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia.
Shau-Ping LinInstitute of Biotechnology, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, 10672, Taiwan.
Chia-Ching WuDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan, 70101, Taiwan. joshccwu@mail.ncku.edu.tw.ORCID http://orcid.org/0000-0001-7224-8425

Funding

National Health Research Institutes NHRI-EX111-10925EINational Science and Technology Council NSTC111-2320-B-006-069-MY2National Science and Technology Council NSTC113-2320-B-006-042-MY3National Science and Technology Council NSTC113-2320-B-006-046
6 · The paper itself

Abstract

backgroundMicroenvironmental alterations induce significant genetic and epigenetic changes in stem cells. Mitochondria, essential for regenerative capabilities, provide the necessary energy for stem cell function. However, the specific roles of histone modifications and mitochondrial dynamics in human adipose-derived stem cells (ASCs) during morphological transformations remain poorly understood. In this study, we aim to elucidate the mechanisms by which ASC sphere formation enhances mitochondrial function, delivery, and rescue efficiency.

methodsASCs were cultured on chitosan nano-deposited surfaces to form 3D spheres. Mitochondrial activity and ATP production were assessed using MitoTracker staining, Seahorse XF analysis, and ATP luminescence assays. Single-cell RNA sequencing, followed by Ingenuity Pathway Analysis (IPA), was conducted to uncover key regulatory pathways, which were validated through molecular techniques. Pathway involvement was confirmed using epigenetic inhibitors or PPARγ-modulating drugs. Mitochondrial structural integrity and delivery efficiency were evaluated after isolation.

resultsChitosan-induced ASC spheres exhibited unique compact mitochondrial morphology, characterized by condensed cristae, enhanced mitochondrial activity, and increased ATP production through oxidative phosphorylation. High expressions of mitochondrial complex I genes and elevated levels of mitochondrial complex proteins were observed without an increase in reactive oxygen species (ROS). Epigenetic modification of H3K27me3 and PPARγ involvement were discovered and confirmed by inhibiting H3K27me3 with the specific EZH2 inhibitor GSK126 and by adding the PPARγ agonist Rosiglitazone (RSG). Isolated mitochondria from ASC spheres showed improved structural stability and delivery efficiency, suppressed the of inflammatory cytokines in LPS- and TNFα-induced inflamed cells, and rescued cells from damage, thereby enhancing function and promoting recovery.

conclusionEnhancing mitochondrial ATP production via the EZH2-H3K27me3-PPARγ pathway offers an alternative strategy to conventional cell-based therapies. High-functional mitochondria and delivery efficiency show significant potential for regenerative medicine applications.

Indexed as

Adipose TissueEnhancer of Zeste Homolog 2 ProteinHistonesMitochondriaPPAR gammaStem CellsAdenosine TriphosphateCells, CulturedChitosanEpigenesis, GeneticHumansReactive Oxygen SpeciesSignal TransductionSpheroids, CellularAdenosine TriphosphateChitosanEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistonesPPAR gammaPPARG protein, humanReactive Oxygen Species3D spheroid cultureAdipose-derived stem cellsChitosan nano-depositionEnhanced mitochondrial functionEZH2-H3K27me3-PPARγ pathwayMitochondrial therapy

Identifiers

PMID40069892
PMCPMC11899936

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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.