Bystander effects induced by irradiated mesenchymal stem cells and their influence on hematopoiesis controls: proliferation, differentiation, maturation, and migration

• Grant number: 24/09422-0
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2024
• End date: November 30, 2027
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Ricardo Ambrósio Fock
• Grantee: Ricardo Ambrósio Fock
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Primavera Borelli Garcia

Abstract

The stem cell (SC) is characterized as a non-specialized cell with the capacity for self-renewal and differentiation, which allows the formation of various tissue types based on external stimuli. Among the different types of SC, there is a stem cell called mesenchymal stem cell (MSC), also known as multipotent mesenchymal stromal cell. This clonogenic cell, initially isolated from the bone marrow, has the ability to form the medullary stroma. Additionally, MSC plays a crucial role in maintaining the hematopoietic microenvironment, regulating other cells through the production of cytokines and growth factors, being able to modulate hematopoiesis. Several malignant diseases, including hematological ones, use ionizing radiation as a therapeutic tool to destroy or prevent the growth of malignant cells, and its use can be done as a neoadjuvant treatment (before surgical or chemotherapy interventions) or as an adjuvant treatment (after surgery or chemotherapy). The direct effects of ionizing radiation are well understood in the literature; however, the impacts on medullary MSCs are little explored. The direct effects of ionizing radiation are well understood in the literature, but little explored on medullary MSCs, representing a critical gap in knowledge. On the one hand, the direct effects of radiation on MSCs are little known; on the other hand, the effects of radiation on cells adjacent to target cells, called the "bystander effect" or "bystander effect", still constitute a completely unknown field. Thus the bystander effect caused by radiation; in biology, refers to a phenomenon in which non-irradiated cells exhibit effects of radiation exposure due to signals received from nearby irradiated cells and this effect challenges the traditional understanding that only directly irradiated cells are affected by radiation, which has implications significant for Radiobiology. In view of the above, and based on data from the literature that contextualize MSCs as important cells for the formation of the medullary microenvironment and consequently with the capacity to modulate the survival, proliferation and development of hematopoietic cells at all their levels of differentiation, this project aims to evaluate the direct influence of radiation on MSCs, as well as the bystander effect in the control of hematopoiesis. To this end, it is proposed to carry out multiple cellular experiments, both in vitro and in vivo, with the aim of evaluating and demonstrating the possible mechanisms involved in these processes. (AU)