Insights from stem cell and hematopoietic stem and progenitor cells (HSPCs) culture for expansion and cell/molecular therapy

• Grant number: 17/14031-6
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2018
• End date: December 31, 2020
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Marcus Alexandre Finzi Corat
• Grantee: Marcus Alexandre Finzi Corat
• Host Institution: Centro Multidisciplinar para Investigação Biológica (CEMIB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Mayara Cristina Moreira Silva

Abstract

The application of stem and progenitor cells in the treatment of diseases is widely reported in the literature, from the production of new tissues through differentiation, as to mitigate of inflammatory process in lesions by regulatory paracrine factors produced by these cell types. However, the understanding of action, treatment, maintenance and manipulation of these cells are still matters that are pending elucidation. Treatments with stem cells and progenitors using ex-vivo genetic orpharmacological tools make cell therapy a promising pathway for curing and treating diseases. The success of bone marrow transplants has only been and is possible due to the presence of hematopoetic stem cells and progenitor cells in the bone marrow that allow the renewal of blood cells. Every stem cell has the characteristic of self-renewing, proliferating and differentiating into functional adult cells. All this process of blood renewal is called hematopoesis and occurs in an orchestrated way inside of the niche. Controlled by a complex signaling through the communication among cytokines released by different cell types found in the niche, which regulate the quiescence, proliferation and differentiation of HSPCs inside the same environment, in the bone marrow. Reproducing all this complexity in vitro for the expansion of HSPCs to regenerative cell therapy is undoubtedly a challenge to be overcome. Nowadays, numerous forms ofcell culture of HSPCs have been proposed and used in different laboratories, but the expansion efficiency for clinical trials is still discouraging. We propose in this work to analyze the regenerative process of newly damaged bone marrow with ionizing radiation in initial recovery periods after transplantation of GFP + traceable HSPCs to obtain some insights. We intend to detect suspected cell types of the medullar niche that would be participating in the regenerative process of the marrow and to test them in culture using more than a supportive cellular type that can collaborate with the ex vivo maintenance and expansion of HSPCs cells. Checking their proliferation, apoptosis and differentiation levels. In addition, we intend to test anti-apoptotic compounds in HSPCs cells that may ameliorate the deleterious process promoted by plasmid transfection and genomic editing with CRISPR-Cas9 in these cells. Opening doors to contribute effectively in the field of biomedical and pharmacological knowledge for the treatment of diseases with the use of cellular and genetic therapies. (AU)