Evaluation of mesenchymal stem cells from human umbilical cord on organ damage and endothelial dysfunction in sepsis

• Grant number: 13/09179-3
• Support type: Scholarships in Brazil - Master
• Effective date (Start): April 01, 2014
• Effective date (End): June 30, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal researcher: Lucia da Conceição Andrade
• Grantee: José Manuel Cóndor Capcha
• Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 10/19012-0 - Evaluation of hematopoietic stem cell treatment in dogs with chronic renal failure, AP.TEM

Abstract

Sepsis is a serious disease in terms of public health. In Brazil, according to the clinical studies, they demonstrate that the country has a high incidence and is projected to continue growing as the old population increase in number. Sepsis is a systemic disease, and many changes are involved. There is an increase in the inflammatory cytokines in an attempt to eliminate the pathogens causing the disease; however, this process also produces systemic hypotension, coagulation disorders, end-organ ischemia and multiple organ dysfunctions.In a model of sepsis with mice, the administration of mesenchymal stem cells (MSCs) promoted decrease in inflammation and also the protection of target organs. MSCs have the ability to migrate to site of injury, reduce local and systemic inflammatory response, inhibit apoptosis in injured tissues, stimulate neoangiogenesis, activate resident populations of stem cells, enhance bacterial clearance and reduce the activity of neutrophils in injured tissue. Most studies of cell therapy with MSC in sepsis demonstrated excited results. However, there are studies with contradictory results, demonstrating that therapy with MSC apoptotic adipose tissue in sepsis decreases the circulating TNF-±, decreases the numbers of T helper cells, cytotoxic T cells and regulatory T cells in both peripheral blood as the spleen, with improvement in survival of animals compared to normal MSCs. This variability may be due to heterogeneity of severe sepsis or the difference between the sources of isolation. It has been known that MSC from different source has different immunoregulatory capacity. We believe that the therapeutic possibilities need more studies before transferring it to the clinical application.Thus, we propose to study in experimental model of sepsis (ligation and puncture of the colon) the protection of human umbilical cord MSCs on renal function. This study will also evaluate heart and immune function. If there is the protection, we are going to study the physiology mechanism involved.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CONDOR, JOSE M.; RODRIGUES, CAMILA E.; MOREIRA, ROBERTO DE SOUSA; CANALE, DANIELE; VOLPINI, RILDO A.; SHIMIZU, MARIA H. M.; CAMARA, NIELS O. S.; NORONHA, IRENE DE L.; ANDRADE, LUCIA. Treatment With Human Wharton's Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction. STEM CELLS TRANSLATIONAL MEDICINE, v. 5, n. 8, p. 1048-1057, AUG 2016. (10/19012-0, 13/09179-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CAPCHA, José Manuel Cóndor. Evaluation of human umbilical cord mesenchymal stem cells in organ damage and endothelial dysfunction in sepsis. 2015. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.