Synergistic effects of laminin-1 peptides, VEGF and FGF9 on salivary gland regeneration

Abstract

Hyposalivation is associated with radiation therapy, Sjogren's syndrome and/or aging, and is a significant clinical problem that decreases oral health and overall health in many patients and currently lacks effective treatment. Hence, methods to regenerate salivary glands and restore saliva secretion are urgently needed. To this end, this study describes the modification of fibrin hydrogels with a combination of laminin-1 peptides (YIGSR and A99) and human growth factors (vascular endothelial growth factor and fibroblast growth factor 9) to enhance regeneration in a salivary gland injury mouse model. Our results indicate that these fortified hydrogels enhanced angiogenesis and neurogenesis while promoting formation of acinar structures, thereby leading to enhanced saliva secretion. Such functional recovery indicates salivary gland regeneration and suggests that our technology may be useful in promoting gland regeneration and reversing hyposalivation in a clinical setting.

P2 Receptors as Therapeutic Targets in the Salivary Gland: From Physiology to Dysfunction

“…Several studies have identified and characterized subsets of endogenous salivary progenitor cells that can be exploited to promote tissue regeneration (Lombaert et al, 2008;Chibly et al, 2014Chibly et al, , 2018Pringle et al, 2016;Emmerson et al, 2018;Weng et al, 2018). The use of modified fibrin hydrogels (Nam et al, 2019a), layered sheets of isolated salivary gland cells released from thermoresponsive culture dishes (Nam et al, 2019b) and salivary organoid cultures generated from embryonic pluripotent stem cells (Tanaka et al, 2018) have been explored as regenerative therapies for damaged salivary glands. Tissue engineering of 3-dimensional (3-D) primary HSG cultures for transplantation into afflicted patients represents another regenerative strategy to restore salivary gland function (Lombaert et al, 2017).…”

Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular Glands

“…The wounded SMG mouse model was created following a method reported previously [ 49 , 50 , 51 , 52 ]. Briefly, female 6-week-old C57BL/6J mice were anesthetized with 3% ( v / v ) isoflurane with an oxygen flow rate of 2.0 L/min.…”

Mouth-Watering Results: Clinical Need, Current Approaches, and Future Directions for Salivary Gland Regeneration

“…Proper vascularisation is essential for endogenous regeneration and for stem cell graft success. While the majority of murine SMG regeneration studies do not report effects on the vascular system, both the drug deferoxamine and laminin-and growth factor-loaded hydrogels improve vascularisation during SMG regeneration [111].…”