Influence of protein deficiency on the mobilization and homing of hematopoietic stem and progenitor cells: Impacts of malnutrition and nutritional recovery

• Grant number: 23/12508-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2025
• End date: September 30, 2028
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Ricardo Ambrósio Fock
• Grantee: Kalil Auzier Martins Costa
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malnutrition appears as a clinical outcome resulting from changes in the intake or absorption of nutrients that culminate in the loss of fat-free mass and body cell mass, which can lead to a decline in physical and mental functions, which characterizes a clinical scenario of disease. . Protein malnutrition (PD) is the most common form of malnutrition and leads to several physiological consequences, particularly in tissues with a high rate of renewal and proliferation, such as hematopoietic tissue. Hematopoiesis is defined as a process by which the cellular constituents of blood are produced and continuously replaced throughout life. At the top of the hematopoietic hierarchy is the long-term hematopoietic stem cell (HSC), which produces all other cell types in the cell ladder. Just below her, the parents. These immature cell types, through marrow mobilization by G-CSF, for example, are of clinical interest for performing bone marrow transplantation in individuals with various pathological hematopoietic conditions. Among the changes caused in hematopoiesis by protein malnutrition, already reported, are: reduction in bone marrow cellularity, expansion of the extracellular matrix and quantitative alteration of some soluble proteins related to cell adhesion in the bone marrow niche (CXCL-12 and SCF, for example). example). In the literature, it is not clear what is the profile of mobilization and medullary homing of immature cells (HSCs and progenitors) in protein malnutrition, nor what are the molecular mechanisms that could alter this mobilization, nor what is the profile and mechanisms involved in nutritional recovery. . Therefore, the objective of this project is to evaluate the effect of protein malnutrition on G-CSF-induced CTH mobilization and CTH homing, and to evaluate possible repercussions on the effectiveness of bone marrow transplantation, as well as to evaluate whether these effects are reversible. after nutritional recovery.