Evidence map›Paper›PMID 39707356›Full record

ArticleJournal of translational medicine2024

TET3-facilitated differentiation of human umbilical cord mesenchymal stem cells into oligodendrocyte precursor cells for spinal cord injury recovery.

Yubo Zhang, Zhibin Peng, Man Guo, Yangyang Wang, Jingsong Liu, Yishu Liu, Mi Li, Tianli Wei, Pengfei Li, Yingwei Zhao and 1 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

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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.

Yubo ZhangDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China.
Zhibin PengDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China.
Man GuoDepartment of Obstetrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, Heilongjiang, China.
Yangyang WangDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China.
Jingsong LiuDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China.
Yishu LiuDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China.
Mi LiDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China.
Tianli WeiDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China.
Pengfei LiDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China.
Yingwei ZhaoDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China.
Yansong WangDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Harbin Medical University, 2075 Qunli Seventh Avenue, Daoli District, Harbin, 150001, Heilongjiang Province, China. wyshmu1975@163.com.ORCID 0000-0002-3688-320X

Funding

Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions ZD2021H003Natural Science Foundation of China 81871781
6 · The paper itself

Abstract

backgroundSpinal cord injury (SCI) inflicts a severe burden on patients and lacks effective treatments. Owing to the poor regenerative capabilities of endogenous oligodendrocyte precursor cells (OPCs) following SCI, there is a growing interest in alternative sources, such as human umbilical cord mesenchymal stem cells (HUCMSCs). TET3 is a key DNA demethylase that plays an important role in neural differentiation, but its role in OPC formation is not well understood. This study aimed to explore the TET3-mediated one-step induction of HUCMSCs into OPCs.

methodsIn vitro, HUCMSCs were induced into OPCs following TET3 overexpression. Changes of methylation and hydroxymethylation during differentiation were monitored, mechanisms involved in the TET3-driven HUCMSC differentiation into OPCs were identified by RNA sequencing. Methylation levels in NG2 and PDGFRA promoter region were detected using Bisulfite Polymerase Chain Reaction (BSP).In vivo, therapeutic effects of iOPCs were evaluated through a rat Allen's SCI model.

resultsThe in vitro analysis confirmed that TET3 enhances HUCMSC differentiation into OPCs, validitied by specific marker expression. The induced OPCs (iOPCs) exhibited methylation and hydroxymethylation patterns similar to native OPCs. BSP analysis demonstrated that TET3 overexpression significantly reduced CpG island methylation in the NG2 and PDGFRA promoter regions. RNA sequencing revealed that TET3 induces iOPCs to express a series of genes essential for OPC formation while inhibiting the signaling pathways that hinder OPC development. In a rat model of SCI, TET3-overexpressing HUCMSCs appear to have the potential to differentiate into iOPCs in vivo, suppressed secondary injury, and promoted functional recovery. The therapeutic effects of iOPCs on SCI were superior to those of standard mesenchymal stem cell treatments.

conclusionsOur study demonstrated that TET3-mediated demethylation reshapes the methylation patterns of HUCMSCs, enabling their efficient one-step conversion into OPCs and significantly reducing the time required for cell preparation. This approach offers a potential strategy for early intervention in SCI. In an SCI model, TET3-induced OPCs contributed to spinal cord repair, providing novel insights into cell therapy strategies for SCI through the lens of methylation regulation.

Indexed as

Cell DifferentiationDioxygenasesDNA MethylationMesenchymal Stem CellsOligodendrocyte Precursor CellsSpinal Cord InjuriesUmbilical CordAnimalsHumansPromoter Regions, GeneticProto-Oncogene ProteinsRatsRats, Sprague-DawleyRecovery of FunctionDioxygenasesProto-Oncogene ProteinsTET3 protein, human5hmCHuman umbilical cord mesenchymal stem cellsInductionOligodendrocyte precursor cellsSpinal cord injuryTET3

Identifiers

PMID39707356
PMCPMC11662714

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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.