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Mesenchymal Stem Cell Therapy in Submandibular Salivary Gland Allotransplantation

Experimental Study

Almansoori, Akram Abdo, MDSc1,2,3; Khentii, Namuun, DDS1; Kim, Bongju, PhD3,4; Kim, Soung-Min, DDS, PhD1,4; Lee, Jong-Ho, DDS, PhD1,3,4,5

doi: 10.1097/TP.0000000000002612
Original Basic Science—General

Background. Allotransplantation of submandibular salivary glands (SMGs) could be an alternative treatment option for severe keratoconjunctivitis sicca in noncandidates for autologous SMG transplantation. This study was conducted to evaluate the effect of allogeneic mesenchymal stem cell (MSC) therapy on the survival of allotransplanted SMGs.

Methods. Thirty-six SMG allotransplantations (n = 6 per group) were performed in New Zealand white rabbits and randomly divided into the following groups: allograft control (Allo-Ctrl), low-dose FK506 (FK506-L), high-dose FK506 (FK506-H), allogeneic MSCs, MSCs+FK506-L, and MSCs+FK506-H. Rabbits were closely observed for 2 weeks. Gland viability and rejection were assessed by monitoring interleukin-2 levels by ELISA, sialoscintigraphy, M3-muscarinic acetylcholine receptor expression, histological evaluation, and apoptosis assay.

Results. Intraoperatively, all glands showed patency and saliva flow except 1 gland. Sialoscintigraphy revealed significantly higher saliva production within the MSC-treated glands. Histologically, MSC-treated glands showed higher glandular tissue preservation and less acini atrophy. The MSCs+FK506-H group revealed significantly lower apoptosis percentage. The highest survival was observed in the MSCs+FK506-H group, followed by the FK506-H and MSCs+FK506-L groups, and lastly less in the FK506-L and MSCs groups.

Conclusions. Concurrent administration of MSCs with FK506-H (0.16 mg/kg) resulted in higher survival rate with greater glandular tissue preservation and salivary secretion. MSCs with FK506-L (0.08 mg/kg) could be an alternative to FK506-H (0.16 mg/kg) in salivary gland allotransplantation.

1 Department of Oral & Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Korea.

2 Department of Oral & Maxillofacial Surgery, Faculty of Dentistry, Sana’a University, Sana’a, Yemen.

3 Clinical Translational Research Center for Dental Science, Seoul National University Dental Hospital, Seoul, Korea.

4 Dental Research Institute, College of Dentistry, Seoul National University, Seoul, Korea.

5 Oral Cancer Center, Seoul National University Dental Hospital, Seoul, Korea.

Received 31 July 2018. Revision received 30 December 2018.

Accepted 1 January 2019.

The study was approved by the Institutional Animal Care and Use Committee (SNU-160720-6-2).

J.-H.L. and A.A.A. participated in the research design. A.A.A., S.M.K., and J.-H.L. participated in the writing of the paper. A.A.A. and N.K. participated in the performance of the research. B.K., S.M.K., A.A.A., and J.-H.L. participated in data analysis.

The authors declare no conflicts of interest.

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C1535).

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

Correspondence: Jong-Ho Lee, DDS, MSD, PhD, Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, 275-1, Yeongun-Dong, Chongro-Ku, Seoul, 110–768, Korea. (

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