Effects of Human Dental Pulp Stem Cell-Derived Conditioned Medium on Atrophied Submandibular Gland after the Release from Ligation of the Main Excretory Duct in Mice

Abstract

The salivary gland duct ligation model for the treatment of obstruction caused by salivary stones causes hypofunction of the salivary gland. However, sufficient results have not been obtained regarding the regeneration of acinar cells and the restoration of function, and the development of treatment methods is still ongoing. Here, we administered dental pulp stem cell-derived conditioned medium (DPSC-CM) containing various growth factors to mice and examined its effects. The main excretory duct of the submandibular gland was ligated; after 3 weeks, the ligation was released, and Dulbecco's modified Eagle's medium (DMEM) or DPSC-CM was administered biweekly via the right jugular vein. The mice were euthanized at 2, 4, and 8 weeks after the release of the ligation, and the submandibular glands were collected. After the release, the acinar cells had a time-dependent recovery. The DPSC-CM group exhibited a significant increase in the expression of progenitor cell marker cytokeratin 5 (CK5) at 4 weeks after the release of the ligation and acinar cell marker aquaporin 5 (AQP5) at 8 weeks compared with the control and DMEM groups by real-time RT-PCR. The administration of DPSC-CM in mice after the release of the submandibular main duct ligation promotes acinar cell regeneration.

Dental Pulp Stem Cells for Salivary Gland Regeneration—Where Are We Today?

“…Besides the transdifferentiation, DPSCs are able to affect acinar cells or immune cells after injection into compromised tissue or intravenously [58,59,79]. Even the supernatants of DPSC cultures offer useful effects on primary acinar cells as well as the immune system [78,83]. While the injection of DPSCs or their supernatants is technically easy, the transplantation of tissueengineered grafts poses the challenge of nerval and vascular supply.…”

“…This approach was investigated by Takeuchi et al [83]. Instead of using DPSCs, they injected conditioned supernatant of a DPSC culture intravenously.…”

“…Instead of using DPSCs, they injected conditioned supernatant of a DPSC culture intravenously. Mice with an induced defect of the Glandula submandibularis subsequently showed an increased regeneration of the SGs compared to the control group [83]. Nevertheless, conditioned supernatants contain several substances that are redundant and have no benefit for the aspired purpose such as antibiotics, fungicides, fetal bovine serum and HEPES.…”

Trends in Salivary Gland Tissue Engineering: From Stem Cells to Secretome and Organoid Bioprinting

“…77 Thus, DPSC-CM have important biological signaling cues for SG regeneration strategies, and the mechanism of action of such factors is currently being investigated by our group and other groups. [75][76][77] However, very few works have evaluated the therapeutic potential of DPSC-CM in comparison with whole DPSC. The biological effect of DPSC-CM and DPSC on odontoblast differentiation was tested and compared.…”