Improving cell-based therapy in Sickle Cell Disease: study of hematopoietic stem cells and progenitors

• Grant number: 20/13391-1
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Simone Kashima Haddad
• Grantee: Simone Kashima Haddad
• 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 researchers: Ana Cristina Silva Pinto ; Fabíola Traina ; Lorena Lôbo de Figueiredo Pontes ; Luiz Guilherme Darrigo Junior ; Tathiane Maistro Malta Pereira ; Thalita Cristina de Mello Costa ; Wassim El Nemer
• Associated research grant(s): 24/01350-0 - Molecular landscapes of the hematopoietic niche: single-cell insights and inflammatory signatures in sickle cell anemia, AP.R

Abstract

The bone marrow microenvironment and its cellular and molecular complexity in sickle cell anemia (SCA) are still poorly understood. SCA is a genetic disease characterized by the synthesis of an altered hemoglobin, HbS. Under hypoxia, HbS polymerizes and results in hemolysis and episodes of vaso-occlusion, leading to important clinical complications, with evident inflammation. The consequences of the constant inflammatory process of SCA, and the conventional treatment (hydroxyurea and transfusion) for the hematopoietic microenvironment, specifically for hematopoietic stem and progenitor cells (HSPCs) are not yet clear. This proposal aims to evaluate the molecular heterogeneity of HSPCs (CD34 +) in the bone marrow of patients with SCA. For that, an integrative approach of gene and protein expression, at the level of individual cells (single-cell RNA sequencing), will be used to understand the effects of systemic inflammation and the action of HU on hematopoiesis. This approach has a translational potential, mainly by assessing the quality of HSPCs for gene therapies, in the context of diseases such as SCA. The results expected in this project may provide the basis for new strategies and therapeutic targets for improving the quality of life of patients, as well as curing SCA. (AU)