Role of inflammatory microenvironment in activation and biology of mesenchymal stem cells

• Grant number: 13/25327-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2014
• End date: June 30, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Danilo Candido de Almeida
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches, AP.TEM
• Associated scholarship(s): 14/18457-0 - Analysis of genome-wide DNA methylation profiles of mesenchymal stem cells during activation induced by inflammatory microenvironment, BE.EP.PD

Abstract

Mesenchymal stem cells (MSC) are defined as fibroblast-like population, which under appropriate conditions, retains the ability to differentiate into a number of cell lineages, including bone, cartilage, tendon, muscle, or adipose tissue. Currently, has been demonstrated that MSCs have powerful immunoregulatory properties on several inflammatory cells (NK, B cell, T cell, macrophages, dendritic cells) and immune regulatory cells (Treg). This MSC abilities is considered very attractive in clinical practice and the use of MSC-based therapies have been explored in a large numerous of inflammatory and non-inflammatory diseases. Although MSC therapy had presented positive results in phase I-II studies, a large randomized study or double-blinded randomized studies did not have demonstrated the same efficacy to inflammatory disorders. Alternatively, have been investigated that MSC possess some key receptors (TLRs, TNFR, INFRs) that could be activated by inflammatory milieu, enhancing MSC immunosuppressive performance. This phenomenon has been investigated in vitro and in vivo using experimental models and some important molecules (TNF-±, INF-³, PAMPs, DAMPs, IDO, iNOS, PGE-2) and signaling pathways (PKR, STAT-1, NF-kB) have been found to participate of this systems, however the precise mechanism behind of MSC activation remain yet little elucidated. Hence, this present study aim to investigate the molecular signature (epigenetic and transcriptome profile) involved during MSC activation by inflammatory microenvironment using distinct kinds of in vitro stimulus.

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)

DE AGUIAR, CRISTHIANE FAVERO; CASTOLDI, ANGELA; ANDRADE-OLIVEIRA, VINICIUS; IGNACIO, ALINE; DA CUNHA, FLAVIA FRANCO; FERREIRA FELIZARDO, RAPHAEL JOSE; BASSI, ENIO JOSE; SARAIVA CAMARA, NIELS OLSEN; DE ALMEIDA, DANILO CANDIDO. Mesenchymal stromal cells modulate gut inflammation in experimental colitis. INFLAMMOPHARMACOLOGY, v. 26, n. 1, p. 251-260, FEB 2018. (13/25327-2, 12/02270-2, 12/16794-3)