DEVELOPMENT OF A CO-CULTURE MODEL OF HUMAN DENTAL PULP STEM CELLS AND MACROPHAGES IN A PRO-INFLAMMATORY ENVIRONMENT FOR THE STUDY OF OSTEOGENESIS IN VITRO

• Grant number: 24/19014-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2025
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Katiúcia Batista da Silva Paiva
• Grantee: Mariana Vitória da Silva e Alves
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells (MSCs) that have been extensively researched for the generation of bone grafts based on bone bioengineering, due to their easy obtainability and high osteogenic differentiation potential. Macrophages are highly plastic immune system cells that can be stimulated to polarize to the M1 (pro-inflammatory) or M2 (anti-inflammatory) profile and play a fundamental role in bone regeneration. The interaction between MSCs and macrophages is part of the emerging area of osteoimmunology. MSCs play a role in the immunoregulation of macrophages during embryonic ossification and bone regeneration. In addition, the pro-inflammatory microenvironment established after a bone injury may contribute to osteogenesis resulting from the MSC-macrophage interaction. Direct and indirect co-culture systems, and two-dimensional (2D) and three-dimensional (3D) cell cultures, such as spheroids, have been used to study these interactions better. Compared to the traditional model, spheroid models aim to mimic the structure and function of the tissue, intensifying osteogenesis and, possibly, being a robust study platform between MSCs-macrophages in vitro. Given the importance of this interaction, we aim to develop a mixed spheroid to study osteoblast differentiation through direct co-culture of DPSCs and macrophages and in a pro-inflammatory environment with TNF-a. (AU)