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Evaluation of hematopoietic regulatory aspects in protein malnutrition: the role of bone marrow endothelial-like cells derived from mesenchymal stem cells

Grant number: 14/06872-2
Support Opportunities:Regular Research Grants
Duration: August 01, 2014 - July 31, 2016
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
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:Amanda Nogueira Pedro ; Primavera Borelli Garcia


Malnutrition remains a major public health problem affecting millions of people worldwide. Previous studies have shown that protein-energy malnutrition (PEM) leads to anemia as a result of the depletion of progenitor hemopoietic populations, changes in cellular development, and also structural and ultrastructural changes in the extracellular matrix. Hematopoiesis occurs in bone marrow (BM) microenvironment region, which regulate the processes of differentiation, proliferation and self- renewal of hematopoietic stem cell (HSC). There are two types of BM microenvironment: endosteal as well as perivascular which has important function in the proliferation and differentiation process. Mesenchymal stem cells (MSC) are responsible for the formation and maintenance of marrow microenvironment, as they give rise to the stromal cells that compose the BM and also contribute to the biochemical composition of the BM environment by secreting growth factors and cytokines. In addition, MSC may be the progenitor cell of BM endothelial cells since they are able to differentiate into these cells when exposed to endothelial growth medium. MSC also exert a regulatory effect on BM endothelial cells. These cells, which are able to modulate BM niche, express proteins that are important for both differentiation and movement of HSC through the BM. In PEM, the regulatory interactions of the marrow perivascular microenvironment on HSC are poorly understood. This project aims to evaluate the possible effects of PEM in the differentiation process of marrow MSC into endothelial cells and also the different capacities of these cells in producing mediators, which are extremely important for the hematopoiesis complex regulation. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
HASTREITER, ARACELI APARECIDA; DOS SANTOS, GUILHERME G.; MAKIYAMA, EDSON NAOTO; SANTOS, ED WILSON CAVALCANTE; BORELLI, PRIMAVERA; FOCK, RICARDO AMBROSIO. Effects of protein malnutrition on hematopoietic regulatory activity of bone marrow mesenchymal stem cells. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 93, . (18/25813-8, 14/06872-2)
HASTREITER, ARACELI APARECIDA; DOS SANTOS, GUILHERME GALVAO; SANTOS, ED WILSON CAVALCANTE; MAKIYAMA, EDSON NAOTO; BORELLI, PRIMAVERA; FOCK, RICARDO AMBROSIO. Protein malnutrition impairs bone marrow endothelial cells affecting hematopoiesis. Clinical Nutrition, v. 39, n. 5, p. 1551-1559, . (18/25813-8, 14/06872-2)
ANTUNES SANTOS, ANDRESSA CRISTINA; CORREIA, CAROLINA ARGONDIZO; DE OLIVEIRA, DALILA CUNHA; NOGUEIRA-PEDRO, AMANDA; BORELLI, PRIMAVERA; FOCK, RICARDO AMBROSIO. Intravenous Glutamine Administration Modulates TNF-alpha/IL-10 Ratio and Attenuates NFkB Phosphorylation in a Protein Malnutrition Model. Inflammation, v. 39, n. 6, p. 1883-1891, . (14/06872-2)
DOS SANTOS, GUILHERME GALVAO; BATOOL, SHAFQAT; HASTREITER, ARACELI; SARTORI, TALITA; NOGUEIRA-PEDRO, AMANDA; BORELLI, PRIMAVERA; FOCK, RICARDO AMBROSIO. The influence of protein malnutrition on biological and immunomodulatory aspects of bone marrow mesenchymal stem cells. Clinical Nutrition, v. 36, n. 4, p. 1149-1157, . (14/06872-2)

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