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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1440974

Human dental pulp stem cells modulate pro-inflammatory macrophages both through cell-tocell contact and paracrine signaling

Provisionally accepted
Monia Maccaferri Monia Maccaferri 1*Alessandra Pisciotta Alessandra Pisciotta 2Gianluca Carnevale Gianluca Carnevale 2Carlo Salvarani Carlo Salvarani 2,3Elisa Pignatti Elisa Pignatti 1,2
  • 1 University Hospital of Modena, Modena, Italy
  • 2 Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con Interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, Università degli Studi di Modena e Reggio Emilia, Modena, Italy
  • 3 Rheumatology Unit, S. Maria Nuova Hospital, IRCCS Local Health Authority of Reggio Emilia, Reggio Emilia, Italy

The final, formatted version of the article will be published soon.

    Macrophages play a key role in most of the inflammatory diseases such as Rheumatoid Arthritis (RA), but the mechanism underlying their pathogenesis is still under study. Among stem cells, human dental pulp stem cells (hDPSCs) have attracted attention due to their easy accessibility and immunomodulatory properties, making them a promising adjuvant therapy. Monocytes, isolated from buffy coats, were differentiated into pro-inflammatory M1 and anti-inflammatory M2 macrophages. Subsequently, they were cultured with hDPSCs either directly or via a cell-culture insert for 48 hours. Finally, they were analyzed for protein and gene expression. In our study, we have demonstrated that, hDPSCs, even without priming, are capable of reducing TNFα levels and enhancing IL-10 release in pro-inflammatory macrophages, both through direct contact and paracrine signaling. Furthermore, we found that their effects are more pronounced when in cell-tocell contact through the decrease of NF-kB and COX-2 expression and of CD80/PD-L1 colocalization. Our work highlights the immunomodulatory properties of hDPSCs on activated proinflammatory macrophages and the potential therapeutic role in inflamed tissue.

    Keywords: Macrophages1, dental pulp stem cells2, inflammation3, cell-culture4, cell-to-cell contact5, paracrine signaling6

    Received: 30 May 2024; Accepted: 23 Sep 2024.

    Copyright: © 2024 Maccaferri, Pisciotta, Carnevale, Salvarani and Pignatti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Monia Maccaferri, University Hospital of Modena, Modena, Italy

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