Evidence map›Paper›PMID 42106917›Full record

ArticleJournal of extracellular vesicles2026

The Small Molecule H89 Facilitates Mesenchymal Stem Cell-derived Extracellular Vesicle Release and Optimizes Therapeutic Efficacy in Liver Regeneration.

Yu Fu, Yi Ma, Jiajun Zhang, Liwei Liang, Ting Li, Zeyi Guo, Zhongzhe Li, Lei Feng, Yi Wang, Guolin He and 5 more

Abstract read
In one paragraph

Article in Journal of extracellular vesicles, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

15 authors.

Yu FuDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.ORCID https://orcid.org/0009-0007-2633-9220
Yi MaDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Jiajun ZhangDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Liwei LiangDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Ting LiDepartment of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Zeyi GuoDepartment of Hepatic Surgery IV, Eastern Hepatobiliary Surgery Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.
Zhongzhe LiDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Lei FengDepartment of Hepatic-Biliary-Pancreatic Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Yi WangShanxi Province Cancer Hospital/ ShanxiHospital Affiliated to Cancer Hospital, Chinese Academy of MedicalSciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China.
Guolin HeDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Shao LiDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Yang LiDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Xiaoping XuDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Hui LiaoDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Yi GaoDepartment of Hepatobiliary Surgery II, GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.ORCID https://orcid.org/0000-0002-4536-6191

Funding

Guangdong S&T Program 2025B1111110001Key Laboratory for Cancer Prevention and treatment of Guizhou Province QKHPT[2025]031National Key Research and Development Program of China 2022YFA1104900National Natural Science Foundation of China 82200702Project of Department of Education of Guizhou Province Qian Jiao Ji[2024] number 105Project of Doctoral Research Fund of the Affiliated Hospital of Guizhou Medical University gyfybsky-2024-44Project of Science and Technology of Guizhou Province Qian Ke He Ji Chu MS[2025]466
6 · The paper itself

Abstract

The role of human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-EVs) in liver regeneration is promising, yet their clinical translation is hampered by insufficient production. Current strategies targeting their secretion are inefficient and lack a clear mechanistic understanding. We isolated and characterized hUCMSC-EVs pretreated with the H89 and other mTORC1 inhibitors. Our findings revealed that H89 effectively enhances the secretion of hUCMSC-EVs across diverse cell types, demonstrating universal efficacy. Importantly, H89 upregulates GABARAPL1 expression, a key negative regulator of the PKA/mTORC1 pathway, to inhibit mTORC1 activity and promote the formation of amphisomes and SNARE-mediated hUCMSC-EVs release. Furthermore, EVs derived from H89-pretreated hUCMSCs (H-EVs) exhibited altered cargo composition, significantly increased proliferative activity, and potentiated liver regeneration via the RELA/miR-29a axis, which regulates the homeostasis of hepatic stellate cells. Our results highlight that H89 enhances hUCMSC-EV secretion through mTORC1 inhibition, with the resulting benefits for liver regeneration mediated by the RELA/miR-29a network. These findings demonstrate the great promise of H89 in EV-based liver regeneration, offering a promising platform for clinical translation.

Indexed as

Extracellular VesiclesLiver RegenerationMesenchymal Stem CellsAnimalsCell ProliferationHepatic Stellate CellsHumansMechanistic Target of Rapamycin Complex 1MicroRNAsUmbilical CordMechanistic Target of Rapamycin Complex 1MicroRNAsamphisomesextracellular vesiclesGABARAPL1H89hepatic stellate cellsliver regenerationmesenchymal stem cellsmiR‐29aRELA

Identifiers

PMID42106917
PMCPMC13157589

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.