Salivary gland organoid transplantation as a therapeutic option for radiation-induced xerostomia.

Autor: Jeon SG; R&D Institute, ORGANOIDSCIENCES Co., Ltd, 331, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea.; Department of Microbiology, CHA University School of Medicine, 335, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea., Lee J; R&D Institute, ORGANOIDSCIENCES Co., Ltd, 331, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea., Lee SJ; R&D Institute, ORGANOIDSCIENCES Co., Ltd, 331, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea.; Department of Microbiology, CHA University School of Medicine, 335, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea., Seo J; R&D Institute, ORGANOIDSCIENCES Co., Ltd, 331, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea., Choi J; R&D Institute, ORGANOIDSCIENCES Co., Ltd, 331, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea., Bae DH; Department of Microbiology, CHA University School of Medicine, 335, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea., Chun DH; Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of Korea., Ko SY; Department of Radiation Oncology, CHA Bundang Medical Center, CHA University, Seongnam, 13496, Republic of Korea., Shin HS; Department of Radiation Oncology, CHA Bundang Medical Center, CHA University, Seongnam, 13496, Republic of Korea., Joo L; Department of Microbiology, CHA University School of Medicine, 335, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea., Lee SH; Department of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 03181, Republic of Korea., Lim YC; Department of Otorhinolaryngology-Head and Neck Surgery, The Research Institute, Konkuk University School of Medicine, 120, Neungdong-ro, Seoul, 05029, Republic of Korea. ycliment@kuh.ac.kr., Choi WH; R&D Institute, ORGANOIDSCIENCES Co., Ltd, 331, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea. whchoi1204@gmail.com.; Department of Microbiology, CHA University School of Medicine, 335, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea. whchoi1204@gmail.com., Yoo J; R&D Institute, ORGANOIDSCIENCES Co., Ltd, 331, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea. jongmanyoo@cha.ac.kr.; Department of Microbiology, CHA University School of Medicine, 335, Pangyo-ro, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea. jongmanyoo@cha.ac.kr.; Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam. jongmanyoo@cha.ac.kr.
Jazyk: angličtina
Zdroj: Stem cell research & therapy [Stem Cell Res Ther] 2024 Aug 26; Vol. 15 (1), pp. 265. Date of Electronic Publication: 2024 Aug 26.
DOI: 10.1186/s13287-024-03833-x
Abstrakt: Background: Xerostomia is a pathological condition characterized by decreased salivation due to salivary gland dysfunction and is frequently attributed to irreversible damage as a side effect of radiation therapy. Stem cell-derived organoid therapy has garnered attention as a promising avenue for resolving this issue. However, Matrigel, a hydrogel commonly used in organoid culture, is considered inappropriate for clinical use due to its undefined composition and immunogenicity. In this study, we aimed to develop a method for culturing collagen-based human salivary gland organoids (hSGOs) suitable for clinical applications and evaluated their therapeutic effectiveness.
Methods: Human salivary gland stem cells were isolated from the salivary gland tissues and cultured in both Matrigel and collagen. We compared the gene and protein expression patterns of salivary gland-specific markers and measured amylase activity in the two types of hSGOs. To evaluate the therapeutic effects, we performed xenogeneic and allogeneic transplantation using human and mouse salivary gland organoids (hSGOs and mSGOs), respectively, in a mouse model of radiation-induced xerostomia.
Results: hSGOs cultured in Matrigel exhibited self-renewal capacity and differentiated into acinar and ductal cell lineages. In collagen, they maintained a comparable self-renewal ability and more closely replicated the characteristics of salivary gland tissue following differentiation. Upon xenotransplantation of collagen-based hSGOs, we observed engraftment, which was verified by detecting human-specific nucleoli and E-cadherin expression. The expression of mucins, especially MUC5B, within the transplanted hSGOs suggested a potential improvement in the salivary composition. Moreover, the allograft procedure using mSGOs led to increased salivation, validating the efficacy of our approach.
Conclusions: This study showed that collagen-based hSGOs can be used appropriately in clinical settings and demonstrated the effectiveness of an allograft procedure. Our research has laid the groundwork for the future application of collagen-based hSGOs in allogeneic clinical trials.
(© 2024. The Author(s).)
Databáze: MEDLINE
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