Evaluation of the combined action of EPO, G-CSF, GM-CSF and IL-3 in the modulation of hematopoiesis in malnourished mice

• Grant number: 17/22407-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2018
• Effective date (End): March 31, 2019
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Ricardo Ambrósio Fock
• Grantee: Beatriz Batista
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Hematopoietic tissue, such as tissues that have a high rate of cell turnover, require a broad source of nutrients and can be altered by deficient nutritional states. Protein malnutrition (PM) compromises lymphohematopoietic organs and modifies the immune response. Our work shows that malnutrition causes anemia and leukopenia. In addition to quantitative changes, we observed qualitative alterations in hematopoietic cells in the bone marrow and peripheral blood and structural and ultrastructural alterations of the bone marrow, spleen and thymus. PM alters the capacity of hematopoietic stem cell (HSC) self-renewal and proliferation, with a greater amount of cells in the G0 and G1 phases of the cell cycle. These processes depend on the medullary microenvironment, an organized structure that regulates the physiology of the stem cell and the hematopoietic progenitors. The cells of the microenvironment produce various cytokines and growth factors that not only modulate the self-renewal, proliferation and differentiation of HSC, but also traffic from mature cells to peripheral blood. By the way, it has already been demonstrated by our group that the medullary microenvironment is compromised in PM, with alteration in the synthesis of hematopoietic stimulating factors. Malnourished animals present severe hypoplasia of hematopoietic organs and compromised production of several important mediators for the production, maturation and mobilization of hematopoietic cells. These animals respond poorly to treatment with EPO and G-CSF alone, however it is now known that the synergism between hematopoietic modulators is of utmost importance for the full functioning of hematopoiesis. Thus, this project aims to evaluate the ability of a stimulant cocktail formed by G-CSF, GM-CSF, IL-3 and EPO to modulate the hematopoiesis of malnourished animals. (AU)