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BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1475473
This article is part of the Research Topic Glycobiology and Glycosylation: Deciphering the Secrets of Glycans in Humans and Pathogens View all 8 articles

Associations between glycan signature alterations and the cellular antigenic properties of passaged chondrocytes

Provisionally accepted
Kentaro Homan Kentaro Homan 1,2,3Taiki Tokuhiro Taiki Tokuhiro 1Tomohiro Onodera Tomohiro Onodera 1*Hisatoshi Hanamatsu Hisatoshi Hanamatsu 4Jun-ichi Furukawa Jun-ichi Furukawa 4Taku Ebata Taku Ebata 1Masatake Matsuoka Masatake Matsuoka 1Ken Kadoya Ken Kadoya 2Mohamad A. Terkawi Mohamad A. Terkawi 1*Norimasa Iwasaki Norimasa Iwasaki 1,2,3
  • 1 Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaidō, Japan
  • 2 Department of Advanced Medicine for Locomotor System, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • 3 Department of Biomaterial Function Regeneration Field, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido University, Sapporo, Japan
  • 4 Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, Aichi, Japan

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

    Background: Cartilage repair is a significant clinical challenge because of the limited intrinsic healing capacity. Current therapeutic strategies, such as cell transplantation therapy, aim to overcome this challenge by replacing damaged tissue with healthy cells. However, the long-term survival and functionality of transplanted cells remain major hurdles.Objective: This study investigated the impact of chondrocyte passaging on glycan profiles and their antigenic properties. We hypothesized that alterations in glycan composition due to passaging may contribute to the enhanced ability to activate macrophages, thereby affecting the outcome of cell transplantation therapy.Methods: Peritoneal macrophages and primary articular chondrocytes were isolated from C57BL/6 mice to establish direct and indirect coculture models. Macrophage activation was assessed by measuring the concentrations of IL-6 and nitric oxide in the culture supernatants or their gene expression. Glycome analysis of various glycoconjugates was performed by glycoblotting methods combined with the SALSA procedure for N-glycans and GSLs and the BEP method for O-glycans.Our results revealed that direct coculture of macrophages with passaged chondrocytes increased the production of proinflammatory cytokines, including IL-6 and NO, as the number of passages increased. With increasing passage number, the expression of GD3 substantially decreased, and the expression of GM3, especially GD1a, significantly increased. Coculturing passaged GM3S knockout chondrocytes with macrophages significantly suppressed IL-6 expression, implying reduced macrophage activation.The observed activation of macrophages due to alterations in the glycan profile of chondrocytes provides a possible explanation for the antigenicity and immune rejection of transplanted cells.

    Keywords: Passage culture, Glycome analysis, Antigenicity, chondrocyte, macrophage, Cellular transplantation

    Received: 03 Aug 2024; Accepted: 06 Nov 2024.

    Copyright: © 2024 Homan, Tokuhiro, Onodera, Hanamatsu, Furukawa, Ebata, Matsuoka, Kadoya, Terkawi and Iwasaki. 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:
    Tomohiro Onodera, Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaidō, Japan
    Mohamad A. Terkawi, Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaidō, Japan

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