Evidence map›Paper›PMID 41526970›Full record

ArticleStem cell research & therapy2026

Hypoxia-conditioned BMSC exosomes improve short-term spinal cord injury outcomes via the miR-615-3p/PDE4C-mediated cAMP/PKA pathway.

Wei Bian, Xiangyu Zeng, Ziwen Liu, Mingyan Guan, Tegeleqi Bu, Haoze Li, Zewei Gao, Jianyu Liu

Abstract read
In one paragraph

Article in Stem cell research & therapy, 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
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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

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

8 authors.

Wei BianDepartment of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Xuefu Road 246, Nangang District, Harbin, 150001, Heilongjiang, China.
Xiangyu ZengDepartment of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Xuefu Road 246, Nangang District, Harbin, 150001, Heilongjiang, China.
Ziwen LiuDepartment of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Xuefu Road 246, Nangang District, Harbin, 150001, Heilongjiang, China.
Mingyan GuanDepartment of Orthopaedics, Northeast International Hospital, Shenyang, 110000, Liaoning, China.
Tegeleqi BuDepartment of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Xuefu Road 246, Nangang District, Harbin, 150001, Heilongjiang, China.
Haoze LiDepartment of Orthopaedics, The Fifth Hospital of Harbin, Harbin, 150040, Heilongjiang, China.
Zewei GaoDepartment of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Xuefu Road 246, Nangang District, Harbin, 150001, Heilongjiang, China.
Jianyu LiuDepartment of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Xuefu Road 246, Nangang District, Harbin, 150001, Heilongjiang, China. liujianyu4@163.com.

Funding

the National Natural Science Foundation of China Grant/Award Number: 81971828
6 · The paper itself

Abstract

Spinal cord injury (SCI) remains a significant global health challenge with limited effective therapeutic options. Exosomes derived from mesenchymal stem cells (MSCs) have emerged as promising neuroprotective agents due to their biocompatibility and immunomodulatory properties. This study investigated the therapeutic potential of hypoxia-conditioned bone marrow MSC (BMSC)-derived exosomes in both in vitro and in vivo SCI models. Hypoxic preconditioning significantly enriched miR-615-3p in bone marrow mesenchymal stem cell (BMSC)-derived exosomes. In spinal neuron injury models, hypoxic exosomes enhanced cell viability, reduced apoptosis, and ameliorated dysfunction of the mitochondria-associated endoplasmic reticulum membranes (MAMs). Mechanistically, miR-615-3p directly targeted and suppressed phosphodiesterase 4 C (PDE4C), activating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. This in turn modulated calcium signaling, attenuated mitochondrial calcium overload, and reduced endoplasmic reticulum stress (ERS). In a mouse model of SCI, short-term treatment with hypoxic exosomes promoted functional recovery within a 14-day post-injury period, as evidenced by improved locomotor performance, reduced lesion volume, attenuated tissue edema, and decreased inflammatory cell infiltration. Furthermore, in vivo administration of hypoxic exosomes upregulated miR-615-3p and downregulated PDE4C expression in injured spinal cord tissues. These results demonstrate that hypoxia-conditioned BMSC-derived exosomes exert neuroprotective effects via the miR-615-3p/PDE4C axis, highlighting their potential as a novel therapeutic strategy for SCI by targeting calcium homeostasis and mitochondrial-ER dysfunction. These findings demonstrate the short-term therapeutic potential of hypoxia-conditioned exosomes in SCI. However, further preclinical studies, including long-term follow-up to assess the durability of recovery and potential late-onset effects, alongside clinical validation, are warranted before clinical translation.

Indexed as

Cyclic AMPCyclic AMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 4ExosomesMesenchymal Stem CellsMicroRNAsSpinal Cord InjuriesAnimalsApoptosisCell HypoxiaDisease Models, AnimalMiceMice, Inbred C57BLSignal TransductionCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 4MicroRNAsBone marrow mesenchymal stem cellsExosomesHypoxia conditioningmiR-615-3pNeuroprotective effectsSpinal cord injury

Identifiers

PMID41526970
PMCPMC12888186

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.