Evidence map›Paper›PMID 40856095›Full record

ArticleAnnals of neurology2025

Intranasal Wharton's Jelly-Derived Mesenchymal Stem Cell Therapy, Alone or in Conjunction With Therapeutic Hypothermia, Alleviates Neonatal Hypoxic-Ischemic Brain Injury in Mice.

Caroline G M de Theije, Sara T De Palma, Josine E G Vaes, Katiuscia Dallaglio, Giorgia Volpi, Diego Ardigò, Sabine van Rijt, Frank van Bel, Manon J N L Benders, Cora H A Nijboer

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Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 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

10 authors.

Caroline G M de TheijeDepartment for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, Utrecht, The Netherlands.ORCID 0000-0003-1265-7897
Sara T De PalmaDepartment for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, Utrecht, The Netherlands.
Josine E G VaesDepartment for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, Utrecht, The Netherlands.
Katiuscia DallaglioGlobal Rare Diseases R&D, Chiesi Farmaceutici S.p.A, Parma, Italy.
Giorgia VolpiGlobal Rare Diseases R&D, Chiesi Farmaceutici S.p.A, Parma, Italy.
Diego ArdigòGlobal Rare Diseases R&D, Chiesi Farmaceutici S.p.A, Parma, Italy.
Sabine van RijtDepartment of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
Frank van BelDepartment of Neonatology, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, Utrecht, The Netherlands.
Manon J N L BendersDepartment of Neonatology, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, Utrecht, The Netherlands.
Cora H A NijboerDepartment for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital, Utrecht University, Utrecht, The Netherlands.ORCID 0000-0003-1223-1861

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveNeonatal hypoxic-ischemic brain injury (HIBI) caused by perinatal asphyxia is a primary cause of long-term neurological morbidity. Hypothermia is the sole available clinical intervention despite its limited efficacy. Intranasal mesenchymal stem cells (MSCs) show promise for the treatment of HIBI. This study explores the efficacy, migration, treatment window, and therapeutic mechanisms of intranasally applied Wharton's jelly-derived MSCs (WJ-MSCs) in a neonatal HIBI mouse model, and assesses its therapeutic benefit in conjunction with hypothermia.

methodsNine-day-old C57BL/6 mice underwent hypoxia-ischemia (HI), with or without hypothermia, and were intranasally dosed with 0.1 to 2.0 × 10

resultsIntranasally delivered WJ-MSCs reduced HI-induced lesion size and sensorimotor impairments. WJ-MSCs expressed multiple receptors for upregulated chemokines in the HI-lesion, and migrated from the nasal cavity into the meninges and brain parenchyma. WJ-MSCs secreted a broad spectrum of immunomodulatory and neuroregenerative proteins, and inhibited neuroinflammation and boosted neuroregeneration in vivo and in vitro. WJ-MSC potency was sustained across different donors. Importantly, intranasal WJ-MSCs augmented the therapeutic benefits of hypothermia following neonatal HIBI in mice.

interpretationThis study provides new translational evidence that intranasal WJ-MSCs, either alone or in combination with hypothermia, mitigate the consequences of neonatal HIBI by resolving inflammation and boosting neurorepair through their secretome. ANN NEUROL 2025;98:1380-1394.

Indexed as

Hypothermia, InducedHypoxia-Ischemia, BrainMesenchymal Stem Cell TransplantationWharton JellyAdministration, IntranasalAnimalsAnimals, NewbornCombined Modality TherapyDisease Models, AnimalMesenchymal Stem CellsMiceMice, Inbred C57BL

Identifiers

PMID40856095
PMCPMC12682942

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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.