Evidence map›Paper›PMID 40659357›Full record

ArticleStem cells translational medicine2025

Mesenchymal stem/stromal cell therapy improves immune recovery in a feline model of severe coronavirus infection.

Patrawin Wanakumjorn, Kazuto Kimura, Diego Castillo, Ehren McLarty, Rachel Formaker, Rachel Qiao, Katherine Farrell, Terza Brostoff, Raneesh Ramarapu, Jully Pires and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cells translational medicine, 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.

  1. Article
  2. Review
  3. Article
  4. Article
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.

Patrawin WanakumjornPathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA.ORCID 0009-0005-4757-0566
Kazuto KimuraPathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA.
Diego CastilloPathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA.
Ehren McLartyVeterinary Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Rachel FormakerPathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA.
Rachel QiaoPathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA.ORCID 0009-0006-6412-8152
Katherine FarrellVeterinary Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Terza BrostoffPathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA.
Raneesh RamarapuVeterinary Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Jully PiresThe Veterinary Center for Clinical Trials, School of Veterinary Medicine, University of California, Davis, CA, USA.
Tamar Cohen-DavidyanThe Veterinary Center for Clinical Trials, School of Veterinary Medicine, University of California, Davis, CA, USA.
Jennifer CassanoThe Regenerative Medicine Laboratory, Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, CA, USA.
Brian MurphyPathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA.
Krystle ReaganVeterinary Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA.
Amir KolPathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA, USA.

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI KC KENT LLOYD · 2002 to 2026
$84.9M
Students Training in Advanced Research (STAR) ProgramT35OD010956 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI DANIKA L BANNASCH · 2012 to 2026
$1.6M
Multi-pronged therapy for immune system regeneration and recovery in a FIP model of MIS-CR21HD106027 · NICHD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KOL, AMIR · 2021 to 2022
$432k
NCI NIH HHS P30 CA093373NICHD NIH HHS R21 HD106027NIH HHS T35 OD010956
6 · The paper itself

Abstract

Severe coronavirus infections, including SARS-CoV-2, are marked by systemic inflammation, T-cell exhaustion, lymphopenia, and chronic immune dysfunction, with limited therapeutic options for recovery. Feline infectious peritonitis (FIP), a naturally occurring feline coronavirus infection, mirrors these immune pathologies, providing a valuable translational model. This study evaluated the safety and efficacy of allogeneic mesenchymal stem/stromal cell (MSC) therapy combined with antiviral treatment in cats with effusive FIP. Hematologic, virologic, and immunologic analyses were conducted over 12 weeks. Antiviral therapy reduced cytotoxic T-cell exhaustion by downregulating inhibitory receptors PD-1, TIM-3, and LAG-3. MSC-treated cats demonstrated enhanced immune recovery, evidenced by reduced expression of exhaustion-related transcription factors (IKZF2, ZEB2, PRDM1) and increased regulatory T-cell populations, promoting immune homeostasis. Single-cell RNA sequencing of mesenteric lymph nodes revealed transcriptomic shifts indicative of immune rejuvenation, including elevated memory T-cell markers (IKZF1, GZMK, IL7R) and reduced hyperproliferative lymphocyte subsets. Serum cytokine analysis revealed 3 distinct inflammatory mediator patterns using principal component analysis. Both treatment groups showed transitions toward cytokine profiles resembling those of healthy controls. Notably, residual cytokine elevations persisted at the study's end, mirroring features of chronic immune dysregulation. PDGF-bb, a marker of tissue repair, was uniquely associated with higher lymphocyte counts, suggesting its role in lymphoid recovery. This study highlights the potential of MSC therapy to modulate immune dysfunction and support durable immune recovery. The findings underscore its translational relevance for addressing severe viral diseases characterized by chronic inflammation and immune dysregulation, advancing both veterinary and human medicine.

Indexed as

COVID-19Feline Infectious PeritonitisMesenchymal Stem CellsMesenchymal Stem Cell TransplantationAnimalsAntiviral AgentsCatsDisease Models, AnimalFemaleMaleSARS-CoV-2T-Lymphocytes, RegulatoryAntiviral Agentsfeline infectious peritonitis (FIP)immune modulationmesenchymal stem/stromal cells (MSCs)severe coronavirus infectionsT-cell exhaustion

Identifiers

PMID40659357
PMCPMC12259234

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.