ArticleCells2023
Immunomodulatory Macrophages Enable E-MNC Therapy for Radiation-Induced Salivary Gland Hypofunction.
Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Wnt/β -catenin signalling shapes macrophage behaviour during injury and repair in the mouse submandibular gland.Scientific reports · 2026Article
- First-in-human study to investigate the safety and efficacy of effective-mononuclear cell therapy for radiogenic xerostomia.Regenerative therapy · 2026Article
- Engineered nanozyme immunomodulator for xerostomia treatment via regulating submandibular salivary gland.Materials today. Bio · 2025Article
- Inhibition of the TLR4/RAGE pathway by clearance of extracellular HMGB1 is a potential therapeutic target for radiation-damaged salivary glands.Regenerative therapy · 2025Article
- Targeted prevention of radiation-induced oral mucositis by glutathione-modified liposome coated K12 probiotics and clinical study.Materials today. Bio · 2025Article
- Immunomodulation of salivary gland function due to cancer therapy.Oral diseases · 2025Review
- Salivary gland macrophages in health and disease: heterogeneity, niche crosstalk, and therapeutic avenues.Frontiers in immunology · 2025Review
- Parotid preservation or immune protection? The dual dilemma in head and neck cancer radiotherapy.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A newly developed therapy using effective-mononuclear cells (E-MNCs) is reportedly effective against radiation-damaged salivary glands (SGs) due to anti-inflammatory and revascularization effects. However, the cellular working mechanism of E-MNC therapy in SGs remains to be elucidated. In this study, E-MNCs were induced from peripheral blood mononuclear cells (PBMNCs) by culture for 5-7 days in medium supplemented with five specific recombinant proteins (5G-culture). We analyzed the anti-inflammatory characteristics of macrophage fraction of E-MNCs using a co-culture model with CD3/CD28-stimulated PBMNCs. To test therapeutic efficacy in vivo, either E-MNCs or E-MNCs depleted of CD11b-positive cells were transplanted intraglandularly into mice with radiation-damaged SGs. Following transplantation, SG function recovery and immunohistochemical analyses of harvested SGs were assessed to determine if CD11b-positive macrophages contributed to tissue regeneration. The results indicated that CD11b/CD206-positive (M2-like) macrophages were specifically induced in E-MNCs during 5G-culture, and Msr1- and galectin3-positive cells (immunomodulatory macrophages) were predominant. CD11b-positive fraction of E-MNCs significantly inhibited the expression of inflammation-related genes in CD3/CD28-stimulated PBMNCs. Transplanted E-MNCs exhibited a therapeutic effect on saliva secretion and reduced tissue fibrosis in radiation-damaged SGs, whereas E-MNCs depleted of CD11b-positive cells and radiated controls did not. Immunohistochemical analyses revealed HMGB1 phagocytosis and IGF1 secretion by CD11b/Msr1-positive macrophages from both transplanted E-MNCs and host M2-macrophages. Thus, the anti-inflammatory and tissue-regenerative effects observed in E-MNC therapy against radiation-damaged SGs can be partly explained by the immunomodulatory effect of M2-dominant macrophage fraction.
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Registered trials
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.