FK506 immunosuppression for submandibular salivary gland allotransplantation in rabbit.

Objectives: We compared the outcomes of two different doses of FK506 (tacrolimus) for immunosuppression in submandibular salivary gland (SMG) allotransplantation. Materials and Methods: Three SMG allotransplantation groups were established (n=6 per group) as follows: allograft rejection control (Allo-Ctrl), low dose (0.08 mg/kg) of FK506 (FK506-L), and high dose (0.16 mg/kg) of FK506 (FK506-H). Allograft survival and rejection were assessed by clinical observation, interleukin-2 levels as determined by enzyme-linked immunosorbent assay, blood sampling for complete blood count (CBC), and histological evaluation. Results: Body weight and anorexia were higher in the FK506-H group but without a significant difference compared with the FK506-L population. CBC revealed a non-significantly reduced number of changes in the FK506-L group. Four glands in the FK506-H group and two glands in the FK506-L group were viable and functioning post-transplantation. Conclusion: The survival rate of allotransplanted glands was higher in conjunction with the high dose of 0.16 mg/kg of FK506, with no major difference in the side-effect profile when compared with the low dose of 0.08 mg/kg short-term outcomes.

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 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.

Rabbit submandibular salivary gland replantation.

OBJECTIVES: To test the feasibility of submandibular salivary gland (SMG) replantation techniques and the survival of the replanted glands. Such a study can provide a rationale for later allotransplantation procedures, along with implementation of conventional and advanced immunosuppression therapy. MATERIALS AND METHODS: Six SMG replantations were performed in New Zealand white rabbits. One week postoperatively, 99mTc scintigraphy was performed and the uptake ratio and salivary excretion fraction were calculated. Two to four weeks later, submandibular glands were excised, fixed, and stained with H&E for histomorphometric evaluation. RESULTS: Intraoperatively, all glands showed patent blood perfusion except gland 5. Positive tracer uptake and saliva excretion were documented by scintigraphy. On excision, all of the glands except glands 4 and 5 looked viable, with a red color and patent pedicles. Gland 4 was infected and filled with creamy pus, while gland 5 looked pale and necrotic. Histologically, glands 1, 2, 3, and 6 had preserved normal glandular tissue with slight variations from the contralateral normal glands, as their parenchyma was composed of mildly atrophic acini. CONCLUSION: Four out of six replanted SMGs successfully survived. The glands maintained good viability and function. Such success depends on safe harvesting, short anastomosis time, and strict control of infection.