Three‐Dimensional Bioprinting Nanotechnologies towards Clinical Application of Stem Cells and Their Secretome in Salivary Gland Regeneration

Abstract

Salivary gland (SG) functional damage and severe dry mouth (or xerostomia) are commonly observed in a wide range of medical conditions from autoimmune to metabolic disorders as well as after radiotherapy to treat specific head and neck cancers. No effective therapy has been developed to completely restore the SG functional damage on the long-term and reverse the poor quality of life of xerostomia patients. Cell- and secretome-based strategies are currently being tested in vitro and in vivo for the repair and/or regeneration of the damaged SG using (1) epithelial SG stem/progenitor cells from salispheres or explant cultures as well as (2) nonepithelial stem cell types and/or their bioactive secretome. These strategies will be the focus of our review. Herein, innovative 3D bioprinting nanotechnologies for the generation of organotypic cultures and SG organoids/mini-glands will also be discussed. These bioprinting technologies will allow researchers to analyze the secretome components and extracellular matrix production, as well as their biofunctional effects in 3D mini-glands ex vivo. Improving our understanding of the SG secretome is critical to develop effective secretome-based therapies towards the regeneration and/or repair of all SG compartments for proper restoration of saliva secretion and flow into the oral cavity.

Involvement of Aquaporins in the Pathogenesis, Diagnosis and Treatment of Sjögren’s Syndrome

“…Renewal of differentiated acinar cells relies on self-duplicating rather than on stem cell differentiation [ 102 ]. Several regenerative strategies have been proposed to restore salivary gland function, including the transplantation of autologous salivary gland-derived epithelial stem cells, the transplantation of non epithelial cell types (such as bone marrow-derived cells, bone marrow-derived mesenchymal stem cells, human adipose-derived mesenchymal stem cells, salivary-gland derived mesenchymal stem cells-like cells, amniotic cells, embryonic stem cells, induced-pluripotent stem cells, and dedifferentiated fat cells), the administration of bioactive compounds (such as growth factors, anti-apoptotic factors, angiogenic factors…), and the transplantation of salivary gland 3D tissue organoids [ 103 , 104 , 105 , 106 , 107 ]. Regenerative cell-based therapies aiming at increasing the number of differentiated acinar cells possessing proper AQP5 protein expression and localization necessary for saliva secretion have significantly progressed.…”

Radiation-associated changes in salivation of patients with cancer of maxillofacial region

“…Доказано, что повышенная концентрация солей стимулирует процесс деминерализации эмали и дентина органическими кислотами, такими как лактат, формиат, пропионат и ацетат, что впоследствии обусловливает возникновение радиоиндуцированного кариеса [37,38]. Однако причинами увеличения концентрации лактата в слюнной жидкости пациентов, получивших лучевое лечение, могут быть также снижение слюноотделения и значительная микробная обсемененность ПР [39,40].…”

Hiposialia y Xerostomía Post Irradiación: Terapias Innovadoras en el Campo Biomolecular

“…Esta se basa en la regeneración, mediante la utilización de células madre, de los tejidos comprometidos por alguna lesión, como es el caso de la inducida por radiación. Ferreira et al (2016) y Lombeart et al 2017, aportan con una clasificación de los enfoques empleados para las terapias: a) células madre epiteliales de glándulas salivales o cultivos de explantes y, b) células madre no epiteliales y/o su secretoma activo. Secretoma es el conjunto de proteínas bioactivas, no rodeadas de membrana, secretadas al espacio intercelular por la propia célula, siendo las más abundantes en el cuerpo humano aquellas de las glándulas salivales (Uhlén et al, 2015).…”