Ensiyeh Kordparijaei, Elaheh Ferdosi-Shahandashti, Zahra Harasani
Mesenchymal stem cells (MSCs) reside in various organs and play vital roles in maintaining tissue homeostasis and facilitating regeneration. These cells can be harvested from discarded tissues, expanded in vitro, and utilized as therapeutic agents for immune-related and inflammatory disorders. Their regenerative capabilities are largely mediated through interactions with immune cells. Dental stem cells (DSCs), isolated from multiple dental tissues, exhibit remarkable immunomodulatory properties and have demonstrated therapeutic efficacy in autoimmune and inflammatory diseases. However, the immunosuppressive function of MSCs/DSCs presents a unique challenge in oncology, where it can paradoxically support tumor progression. This review critically analyzes the immunoregulatory pathways involved in inflammatory and immune-related disorders, and directly links these mechanisms to the challenges within the tumor microenvironment. Furthermore, we discuss innovative bioengineering strategies to reprogram MSCs/DSCs or target their pathways for enhanced anticancer efficacy. We highlight the critical clinical limitations and the need for personalized approaches based on distinct DSC subpopulations. A deeper comprehension of this context-dependent functionality is essential for developing safe and effective MSC/DSC-based therapies.