Mesenchymal Stem Cell Therapy in Submandibular Salivary Gland Allotransplantation: Experimental Study

Background. Allotransplantation of submandibular salivary glands (SMGs) could be an alternative treatment option for severe keratoconjunctivitis sicca in non-candidates for autologous submandibular salivary gland 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 (NZW) 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 two weeks. Gland viability and rejection were assessed by monitoring interleukin-2 (IL-2) levels by enzyme-linked immunosorbent assay (ELISA), sialoscintigraphy, M3-muscarinic acetylcholine receptor (M3 receptor) expression, histological evaluation, and apoptosis assay. Results. Intraoperatively, all glands showed patency and saliva flow except one 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. MSCs+FK506-H group revealed significantly lower apoptosis percentage. The highest survival was observed in the MSCs+FK506-H, followed by the FK506-H and MSCs+FK506-L, 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) in salivary gland allotransplantation. IACUC approval: The study was approved by the Institutional Animal Care and Use Committee (IACUC) (SNU-160720-6-2) Disclosure: The authors declare no conflicts of interest. Funding: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI15C1535). Corresponding author: 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. leejongh@snu.ac.kr, Phone +82-2-2072-2630, Mobile +82-10-3772-7353, Fax +82-2-766-4948 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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