Evaluation of aging in the paracrine repair mechanism of stem cells in the nephrotoxic acute injury.

• Grant number: 18/20139-7
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): November 01, 2018
• Effective date (End): February 28, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mirian Aparecida Boim
• Grantee: Márcia Bastos Convento
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 15/23345-9 - MicroRNAs, extracellular vesicles and stem cells: physiology, pathophysiological role and therapeutic potential in renal diseases, AP.TEM

Abstract

Acute renal failure (ARF) is a common clinical syndrome. Drug-induced renal injury is one of the most common causes of ARF, especially in Intensive Care Units. Among the various nephrotoxic agents, there may be mentioned bactericidal aminoglycoside antimicrobials, such as gentamicin. The main target of renal injury induced by these antibiotics is the proximal tubular cell, which is highly sensitive to nephrotoxic injury and concentrates the antibiotic in the intracelular environment. Stem cells have been extensively studied in acute renal injury. Among the various types of stromal mesenchymal cells, those with the greatest proliferation capacity are those derived from the umbilical cord. Regardless of the subtypes of stromal cells (bone marrow, hematopoietic, umbilical cord or adipose tissue) the protective mechanism appears to be predominantly paracrine and mediated by microvesicles. Exosomes are one of the types of vesicles released by cells, carry RNAs and microRNAs that participate in the mechanism of communication and repair of cell damage. It has already been shown that the protective effect of microvesicles derived from endothelial progenitor cells in AKI was mediated by proangiogenic microRNAs. The aging process in an animal deteriorates several biological functions, however the effect of aging on the production and action of these microvesicles and their carried microRNAs has not yet been explored. The main objective of this work is to evaluate the effect of aging on the protective mechanism of exosomes derived from umbilical cord and boné marrow stromal cells in the antibiotic-induced lesion in proximal tubular cells.