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

JaeYoul Lim, Tacghee Yi, Jeong Seok Choi, Yun Ho Jang, Songyi Lee, Hun Jung Kim, Sun U. Song, Young Mo Kim

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)136-143
Number of pages8
JournalOral Oncology
Volume49
Issue number2
DOIs
Publication statusPublished - 2013 Feb 1

Fingerprint

Salivary Glands
Bone Marrow Transplantation
Mesenchymal Stromal Cells
Bone Marrow
Transplantation
Xerostomia
Cell- and Tissue-Based Therapy
Salivation
Acinar Cells
Head and Neck Neoplasms
Microvessels
Inbred C57BL Mouse
Confocal Microscopy
Neck
Epithelial Cells
Radiation
Staining and Labeling
Control Groups

All Science Journal Classification (ASJC) codes

  • Oral Surgery
  • Oncology
  • Cancer Research

Cite this

Lim, JaeYoul ; Yi, Tacghee ; Choi, Jeong Seok ; Jang, Yun Ho ; Lee, Songyi ; Kim, Hun Jung ; Song, Sun U. ; Kim, Young Mo. / Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage. In: Oral Oncology. 2013 ; Vol. 49, No. 2. pp. 136-143.
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abstract = "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.",
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Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage. / Lim, JaeYoul; Yi, Tacghee; Choi, Jeong Seok; Jang, Yun Ho; Lee, Songyi; Kim, Hun Jung; Song, Sun U.; Kim, Young Mo.

In: Oral Oncology, Vol. 49, No. 2, 01.02.2013, p. 136-143.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage

AU - Lim, JaeYoul

AU - Yi, Tacghee

AU - Choi, Jeong Seok

AU - Jang, Yun Ho

AU - Lee, Songyi

AU - Kim, Hun Jung

AU - Song, Sun U.

AU - Kim, Young Mo

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N2 - 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.

AB - 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.

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