IADR Abstract Archives
Secretome from Human Dental Pulp Stem Cells Exhibits Therapeutic Potential for Salivary Gland Regeneration after Radiotherapy
Objectives: Radiotherapy, the elective therapy for head and neck cancers, can irreversibly damage the secretory epithelial cells from salivary glands (SG) in about 40% of patients. This damage results in xerostomia, which increases the susceptibility to oral infections, decreasing the quality of life of patients. Current options for dry mouth therapies are dependent on both the limited number of residual SG secretory cells and on available stem cell cryopreserved banks from each individual. Hence, the development of non cell-based approaches is essential to regenerate the damaged SG epithelia when stem cell sources are scarce. Thus, our aim was to generate noncell-based methodologies to regenerate or repair the SG.
Methods: Undifferentiated human dental pulp stem cells (hDPSC) were expanded as regular monolayer cultures from passages 1 through 7. Cells were characterized genotypically and phenotypically through these passages by qPCR, whole-mount immunofluorescence and flow cytometry. Cell population doublings, functional calcium and ATP activities were assessed to determine cellular proliferation, metabolism and viability. Delivery of different secretome concentrations into ex vivo SG xerostomia rodent models (fetal SG from ICR mice previously damaged by radiotherapy) was performed. Branching morphogenesis, epithelial growth, cell turnover and the Sox2-positive stem cell niche were evaluated.
Results: Human DPSC maintained their mesenchymal adult stem cell properties through passaging and were highly proliferative with normal metabolic status. The secretome derived from hDPSC was able to restore the epithelial growth of irradiated SG glands by increasing both the pro-mitotic (Ki67) cell niche in the acinar epithelial compartment and the Sox2-positive stem cell niche.
Conclusions: This research work offers a promising therapeutic solution that is secretome-based to alleviate xerostomia in cancer patients who undergo radiotherapy. Future directions will focus on continuing these studies on small and large in vivo models that can better mimic the human SG.
Methods: Undifferentiated human dental pulp stem cells (hDPSC) were expanded as regular monolayer cultures from passages 1 through 7. Cells were characterized genotypically and phenotypically through these passages by qPCR, whole-mount immunofluorescence and flow cytometry. Cell population doublings, functional calcium and ATP activities were assessed to determine cellular proliferation, metabolism and viability. Delivery of different secretome concentrations into ex vivo SG xerostomia rodent models (fetal SG from ICR mice previously damaged by radiotherapy) was performed. Branching morphogenesis, epithelial growth, cell turnover and the Sox2-positive stem cell niche were evaluated.
Results: Human DPSC maintained their mesenchymal adult stem cell properties through passaging and were highly proliferative with normal metabolic status. The secretome derived from hDPSC was able to restore the epithelial growth of irradiated SG glands by increasing both the pro-mitotic (Ki67) cell niche in the acinar epithelial compartment and the Sox2-positive stem cell niche.
Conclusions: This research work offers a promising therapeutic solution that is secretome-based to alleviate xerostomia in cancer patients who undergo radiotherapy. Future directions will focus on continuing these studies on small and large in vivo models that can better mimic the human SG.