Self-renewal, plasticity, senescence and death of mesenchymal stem cells from bone marrow from animals with Sepsis: therapeutic potential and evaluation

• Grant number: 16/13406-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2017
• End date: August 26, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Francisco Garcia Soriano
• Grantee: Thatiana Corrêa de Melo
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/04138-2 - Sepsis and LPS tolerance - LPS tolerance role on oxidative stress and mithocondrial function, proteic nytrosilation and DNA damage, AP.TEM

Abstract

Stem Cells (SCs) are cells with high proliferation capacity, self-renewal and ability to differentiate into more specialized cell lines. Adult CTs, such as Mesenchymal Stem Cells (MSCs) are of great interest for regenerative medicine, mainly in replacement tissues and transplants, such as bone marrow. MSCs are easy to obtain and have high proliferative capacity in vitro. These cells offer a wide range of molecular and chemical compounds in vitro culture system, in addition to having a broad immunoregulatory capacity. These features have been exploited in different experimental models for preventing and treating autoimmune and inflammatory disorders in which is included the Sepsis. Sepsis is a systemic inflammatory response that is unorganized and exacerbated, deriving from infectious processes that eventually develops into septic shock. Positive therapeutic effect of MSCs in animal models with Sepsis has already been described, but there is little information relating the influence of Sepsis in mesenchymal stem cells and deepest investigation is needed. In this context, in the present work we propose to investigate the interaction of sepsis with MSCs, especially regarding the possible changes of self-renewal characteristics, plasticity, senescence and death. For that, MSCs derived from bone marrow of animals with Sepsis induced by Cecal Ligation and Puncture (CLP) will be obtained. Moreover, the therapeutic potential of these cells in CLP animal models will be evaluated. Immunological patterns and the ability to protect fromt the degeneration caused by Sepsis will be examined. (AU)