Amnion mesenchymal stem cell metabolites reduce inflammation in diabetic salivary gland defect rat models

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Diah Savitri Ernawati, Karlina Puspasari, Gremita Kusuma Dewi, Desiana Radithia, Nurina Febriyanti Ayuningtyas, Reiska Kumala Bakti, Satutya Wicaksono, Meircurius Dwi Condro Surboyo, Madhu Shrestha, Alexander Patera Nugraha, Igo Saiful Ihsan, Wibi Riawan, Annissaqiella Maharani, Sri Dewanthy Putri, Adhistya Viany

2025 Journal of Oral Biology and Craniofacial Research Vol. 15 Issue 6 Article Cited by 0 Quartile

Abstract

Objectives: Hyposalivation or xerostomia are well-established intraoral complications of diabetes mellitus (DM). Amniotic Mesenchymal Stem Cell Metabolite Products (AMSC-MPs) are being widely studied for their immunomodulatory action. However, their potential in a salivary gland defect model has yet to be explored. This study aims to determine the potential of AMSC-MPs in modulating the inflammatory response in the salivary glands of rats with persistent hyperglycemia, mimicking the pathogenesis of salivary gland disorders in DM. Methods: Forty-eight male pre-conditioned diabetic rats were divided into treatment and control groups. The treatment group received AMSC-MPs intraglandular injections, while the control group received phosphate-buffered saline intraglandular injections. Both groups were injected for 3, 5, 7, and 10 consecutive days. Subsequently, the submandibular salivary glands were biopsied and processed for formalin-fixed paraffin-embedded tissue for immunohistochemical assessment. The inflammatory response was assessed by quantifying the expression of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), and transforming growth factor β (TGF-β). Results: This study found significant downregulation of inflammatory cytokines, TNF-α and IL-6, in the AMSC-MPs intraglandular injections compared to the control (p < 0.05). Moreover, IL-10 and TGF-β expression, which may act as anti-inflammatory cytokines in this pathology, was significantly upregulated compared to the control (p < 0.05). Conclusion: Our study demonstrated the anti-inflammatory potential of AMSC-MPs intraglandular injections in a diabetes-induced salivary gland defect rat model. © 2025 The Authors. Published by Elsevier B.V. on behalf of Craniofacial Research Foundation. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/

Affiliations

Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Oral Medicine Specialist Study Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Department of Oral and Maxillofacial Pathology, Faculty Diagnostic Science, School of Dentistry, Texas A&M University, TX, United States; Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; Stem Cell Research and Development Center, Universitas Airlangga, Surabaya, Indonesia; Faculty of Medicine, Brawijaya University, Malang, Indonesia