A Pilot Study to Assess the Salivary Gland Regenerative Potential of Bone Marrow Mesenchymal Stromal Cells from Treated Head and Neck Cancer Patients

Background: Salivary dysfunction is a significant side effect of radiation therapy for head and neck cancer (HNC). Preliminary data suggests that mesenchymal stromal cells (MSCs) can improve salivary function. Whether MSCs from HNC patients who have completed chemoradiation are functionally similar to those from healthy patients is unknown. We performed a pilot clinical study to determine whether bone marrow-derived MSCs (BM-MSCs) from HNC patients could be used for the treatment of RT-induced salivary dysfunction.Methods: An IRB-approved pilot clinical study was untaken on HNC patients with xerostomia who had completed treatment two or more years prior. Patients underwent iliac crest bone marrow aspirate and BM-MSCs were isolated and cultured. Culture expanded BM-MSCs were stimulated with IFNγ and cryopreserved prior to reanimation and profiling for functional markers by flow cytometry and ELISA. BM-MSCs were additionally injected into mice with radiation-induced xerostomia and the changes in salivary gland histology were examined. Results: A total of six subjects were enrolled. BM-MSCs from all subjects were culture expanded to >20 million cells in a median of 15.5 days (range 8-20 days). Flow cytometry confirmed that cultured cells from HNC patients were BM-MSCs. Functional flow cytometry demonstrated that these IFNγ-stimulated BM-MSCs acquired an immunosuppressive phenotype. IFNγ-stimulated BM-MSCs from HNC patients were found to express GDNF, WNT1, and R-spondin 1 as well as pro-angiogenesis and immunomodulatory cytokines. In mice, IFNγ-stimulated BM-MSCs decreased the loss of acinar cells decreased the formation of fibrosis. Conclusions: BM-MSCs from previously treated HNC patients can be expanded for auto-transplantation and are functionally active. Furthermore, IFNγ-stimulated BM-MSCs express proteins implicated in salivary gland regeneration. This study provides preliminary data supporting the feasibility of using autologous BM-MSCs from HNC patients to treat RT-induced salivary dysfunction.Trial Registration: NCT04007081, Registered July 5, 2019, https://clinicaltrials.gov/ct2/show/NCT04007081