Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage

• Published in: Oral oncology Vol. 49; no. 2; pp. 136 - 143
• Main Authors: Lim, Jae-Yol, Yi, TacGhee, Choi, Jeong-Seok, Jang, Yun Ho, Lee, Songyi, Kim, Hun Jung, Song, Sun U, Kim, Young-Mo
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-02-2013; Elsevier
• Subjects: Animals; Biological and medical sciences; Body Weight; Cell Differentiation; Cell Survival; Head and neck neoplasms; Hematology, Oncology and Palliative Medicine; Immunohistochemistry; Medical sciences; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Otolaryngology; Otorhinolaryngology. Stomatology; Radiotherapy; Salivary glands; Salivary Glands - pathology; Salivary Glands - physiopathology; Salivary Glands - radiation effects; Stem Cell Transplantation; Tumors; Xerostomia; Salivary glands; Radiotherapy; Head and neck neoplasms; Xerostomia; Mesenchymal stem cells; Stomatology; Stem cell; Salivary gland; ENT; Transplantation; Salivary gland disease; Cancerology; Treatment; Surgery; Bone marrow; Head and neck; Graft; ENT disease; Tumor; Lesion; Aptyalism
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2012.08.010

Summary Objectives External irradiation in head and neck cancers may induce irreversible hyposalivation and consequent xerostomia, stemming from radiation damage to salivary glands (SGs). As cell-based therapy has been reported to be able to repair or restore damaged SG tissues, we attempted to determine whether bone marrow-derived clonal mesenchymal stem cells (BM-cMSCs) can ameliorate irradiation-induced salivary gland damage via a murine model. Methods External irradiation at a dose of 15 Gy was delivered to the neck fields of C57BL/6 mice. We directly administered either homologous mouse BM-cMSCs labeled with PKH26 (treatment group) or PBS (control group) into SGs 24 h after irradiation. Salivary flow rate (SFR) and lag time of salivation were measured at 12 weeks after transplantation. At 4 and 12 weeks post-transplantation, we performed morphological, histological, and immunofluorescent examinations. Transdifferentiation of administered BM-cMSCs into salivary epithelial cells was observed by confocal microscopy. Results SFR was significantly increased in BM-cMSCs-transplanted mice compared with PBS-injected mice at 12 weeks after transplantation. Administration of BM-cMSCs preserved the microscopic morphologies of SGs, with more functional acini in BM-cMSC-transplanted SGs than in PBS-injected SGs. Immunofluorescent staining revealed less apoptotic cells and increased microvessel density in BM-cMSC-transplanted SGs compared with PBS-injected SGs. PKH-26 labeled BM-cMSCs were detected in transplanted SGs at 4 weeks after transplantation and in vivo transdifferentiation of BM-cMSCs into acinar cells was also observed. Conclusion This study suggests that BM-cMSCs can ameliorate salivary damage following irradiation and can be used as a source of cell-based therapy for restoration of irradiation-induced salivary hypofunction.