ANALYSIS OF THE POLARIZED MACROPHAGES EFFECT ON REGENERATIVE CHARACTERISTICS OF EXOSOMES SECRETED BY HUMAN DENTAL PULP STEM CELLS IN THE EARLY STAGES OF BONE DIFFERENTIATION

• Grant number: 23/13702-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2024
• End date: November 30, 2028
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Katiúcia Batista da Silva Paiva
• Grantee: Daniel Barrozo Ferreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Communication between macrophages (MÆ) and mesenchymal stem cells (MSCs) is fundamental to bone regeneration process. Shortly after the injury, there is a MÆM1 (pro-inflammatory) predominance, recruiting cells such as MSCs, and secreting molecules that stimulate the inflammatory process. Over time, and with the influence of MSCs exosomes, a transition to the MÆM2 (anti-inflammatory) phenotype occurs. The change in macrophage polarization in the lesion appears to be important for driving bone differentiation in MSCs, with the MÆM1 phenotype stimulating this process initially, while the MÆM2 phenotype, later. Since the secretome of these polarized macrophages can also alter the composition of the exosomes of differentiating MSCs, it is possible that they are responsible for modulating their regenerative capabilities. Exosomes with regenerative properties can be incorporated into tissue engineering approaches, such as biomimetic bone grafts, and thus assist in the bone repair process. Adult human dental pulp stem cells (DPSCs) are a type of MSC promising for craniofacial reconstruction, they are more prone to osteoblastic differentiation than other MSCs, in addition have high anti-inflammatory capacity. The cultivation of MSCs in the form of a spheroid (3D) better mimics the tissue microenvironment and increases the regenerative capacity of the cells, which could enhance these characteristics in exosomes. Thus, the objective of this project is to evaluate the effect of the polarized macrophage secretome on the pro-regenerative characteristics of exosomes secreted by DPSC spheroids during the initial stages of bone differentiation.