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      TMSC 유래 침샘 세엽세포 스페로이드의 개발 및 약물 유도 하악하선 손상 모델에서의 응용

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      다국어 초록 (Multilingual Abstract) kakao i 다국어 번역

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      Salivary gland dysfunction significantly impairs oral health and quality of life. Conventional treatments are often palliative and fail to restore glandular function. In this study, we aimed to develop a regenerative approach by generating salivary acinar-like spheroids from tonsil-derived mesenchymal stem cells (TMSCs). TMSC spheroids were cultured and primed using a combination of fibroblast growth factor 10 (FGF10) and DAPT, a Notch signaling inhibitor. This priming strategy significantly enhanced AQP5 expression, confirming a lineage bias toward an acinar phenotype. To assess therapeutic efficacy, a submandibular gland injury model was established in mice using the chemotherapeutic agent pemetrexed (PMX). PMX induced notable damage to serous acinar cells, marked by dislocated AQP5 expression and histological vacuolization. Implantation of the primed spheroids into the damaged glands led to increased serous acini regeneration, restoration of overall AQP5 expression, and increase in salivary flow. Overall, this study provides a foundation for stem cell-based, acinar-targeted regeneration of damaged salivary glands.
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      Salivary gland dysfunction significantly impairs oral health and quality of life. Conventional treatments are often palliative and fail to restore glandular function. In this study, we aimed to develop a regenerative approach by generating salivary ac...

      Salivary gland dysfunction significantly impairs oral health and quality of life. Conventional treatments are often palliative and fail to restore glandular function. In this study, we aimed to develop a regenerative approach by generating salivary acinar-like spheroids from tonsil-derived mesenchymal stem cells (TMSCs). TMSC spheroids were cultured and primed using a combination of fibroblast growth factor 10 (FGF10) and DAPT, a Notch signaling inhibitor. This priming strategy significantly enhanced AQP5 expression, confirming a lineage bias toward an acinar phenotype. To assess therapeutic efficacy, a submandibular gland injury model was established in mice using the chemotherapeutic agent pemetrexed (PMX). PMX induced notable damage to serous acinar cells, marked by dislocated AQP5 expression and histological vacuolization. Implantation of the primed spheroids into the damaged glands led to increased serous acini regeneration, restoration of overall AQP5 expression, and increase in salivary flow. Overall, this study provides a foundation for stem cell-based, acinar-targeted regeneration of damaged salivary glands.

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      목차 (Table of Contents)

      • Ⅰ. Introduction 1
      • Ⅱ. Materials and Methods 3
      • 2.1 Isolation, culture, and characterization of human TMSCs 3
      • 2.2 TMSC spheroids formation and priming 4
      • 2.3 Animal modeling and implantation 6
      • Ⅰ. Introduction 1
      • Ⅱ. Materials and Methods 3
      • 2.1 Isolation, culture, and characterization of human TMSCs 3
      • 2.2 TMSC spheroids formation and priming 4
      • 2.3 Animal modeling and implantation 6
      • 2.4 Histological analysis 6
      • 2.5 Protein analysis 7
      • 2.6 Statistical analysis 8
      • Ⅲ. Results 9
      • 3.1 Spheroid characterization 9
      • 3.2 Salivary gland damaged induced by pemetrexed 15
      • 3.3 Recovery effects of primed spheroid implantation 20
      • Ⅳ. Discussion 29
      • V. Conclusion 31
      • References 32
      • Korean Abstract 35
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