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Immunophenotypic and functional analysis of circulating CD34 cells in patients with sickle cell anemia under chronic transfusion or Hydroxyurea regimen.

Grant number: 22/09643-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2022
Effective date (End): September 30, 2024
Field of knowledge:Biological Sciences - Biology
Principal Investigator:Simone Kashima Haddad
Grantee:Yasmin Lima dos Santos Teixeira
Host Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil
Associated research grant:13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID

Abstract

Sickle cell anemia (SCA) is a disease in which a point mutation in the beta-globin chain (HbB) gene, type A - T, leads to the synthesis of "S" globins and formation of hemoglobins (HbS) that polymerize within the red blood cells, changing their biconcave structure making them sickle. These cells present greater dehydration and endothelial adhesion, in addition to a high degree of hemolysis and risk of vascular occlusion. These cellular manifestations continually lead to the most common pathological features of the disease: systemic inflammation, vaso-occlusive crises, and anemia. Currently, there are few treatments for sickle cell anemia and all have some kind of limitation. Among them is hydroxyurea (HU), an antineoplastic drug that increases levels of fetal hemoglobin (HbF) in erythrocytes. In FA, HU has an indirect effect on decreasing HbS polymerization by increasing HbF, in addition to decreasing inflammation and intercellular adhesion. However, this drug limits the growth, differentiation potential and frequency of hematopoietic stem and progenitor cells (HSPC) and bone marrow niche cells. This disruption may restrict patients chances of access to bone marrow transplantation (and gene therapy), the only potentially curative therapy. Thus, the objective of this work is to evaluate the immunophenotypic and functional patterns of populations of circulating HSPCs of individuals with FA, treated or not with HU. Therefore, peripheral blood mononuclear cells will be evaluated by flow cytometry and qPCR for the expression of important adhesion markers in hematopoiesis such as CD44 and CD49d. In addition, different populations of HSPCs will be subjected to in vitro differentiation for cell functional analysis. At the end of this study, it is expected to obtain functional integrity biomarkers of HSPCs from individuals with SCA, in addition to possible new strategies for stem cell selection for transplantation and gene therapy.

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