Cellular characterization of hematopoietic niches in murine model of sickle cell anemia

• Grant number: 19/22155-2
• Support type: Scholarships in Brazil - Master
• Effective date (Start): January 01, 2020
• Effective date (End): April 30, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Simone Kashima Haddad
• Grantee: Felipe Augusto Rós
• Home 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

The hematopoietic niche is a highly dynamic, orchestrated and heterogeneous microenvironment for the cell types that make up. This microenvironment acts on the regulation of the hematopoietic system, which is the controller of the production of all the blood cells of the organism in homeostasis or stress. Among the cell types that make up the niche, there are Multipotent Mesenchymal Stromal Cells (MSC) that, alongside other cell components, support and regulate self-renewing of Hematopoietic Stem Cells (HSC). The study of bone marrow MSC of individuals affected by other hematological disorders, such as humans and murine model affected by aplastic anemia and Fanconi anemia, respectively, revealed morphofunctional changes in these cells. This project aims to investigate the changes caused by sickle cell anemia (SCA) in the cell populations of the splenic intramedullary and extramedullary hematopoietic niche of transgenic mice used as a model for the study of the disease and to analyze morphofunctionaly the MSC present in these niches. For this, hematopoietic and stromal cell populations of the MO and spleen will be described. Additionally, MSCs will be characterized in vitro as to their morphofunctional characteristics related to the maintenance and regulation of HSC in SCA. The characterization of the sickle cell hematopoietic niche will allow the future use of this model in studies that evaluate the effect of known or potential drugs on the niche. In addition, it enables the development and analysis of new HSC transplantation protocols, adjuvant cell therapy or gene therapy. (AU)