Secretome of osteogenic spheroid from dental pulp stem cells influences of on the immunomodulatory potential in cells of the immune system

Abstract

The so-called "bottom-up" approach within bone tissue bioengineering has gained more and more attention recently, as, unlike the classic or "top-down" approach, it manages to better recreate three-dimensional cell structures that enable greater cell-cell and cell-extracellular matrix (MEC) interaction, similar to what is found in vivo. Thus, these structures, such as spheroids, are able to enhance the regenerative properties of mesenchymal stem cells (MSC). Among them, human adult dental pulp-derived cells (DPSCs) are attractive for craniofacial bone reconstruction due to the embryological origin of cells in this tissue. DPSCs secrete a wide range of biofactors that together are called secretomes. This material is rich in trophic factors that communicate with different cell types, including those of the innate immune system, leading to different biological responses. Thus, the bioactive molecules that constitute the secretome are responsible for its immunomodulatory potential, being able to polarize macrophages to the "alternative" M2 phenotype, which differs from the "classic" M1 pro-inflammatory phenotype, as it is characteristic of being anti-inflammatory and pro-tissue regeneration in vitro. It is known that the bone tissue regeneration process undergoes a pro-inflammatory and hypoxia phase and that these conditions affect the polarization capacity of macrophages. Therefore, the main goal of this project is to evaluate the influence of DPSC spheroids secretome on the capacity to modulate macrophage polarization, in an osteogenic environment and in pro-inflammatory and hypoxia conditions.(AU)