The influence of protein malnutrition on biological and immunomodulatory aspects of bone marrow mesenchymal stem cells

Author(s)

dos Santos, Guilherme Galvao ; Batool, Shafqat ; Hastreiter, Araceli ; Sartori, Talita ; Nogueira-Pedro, Amanda ; Borelli, Primavera ; Fock, Ricardo Ambrosio

• Document type: Journal article
• Source: Clinical Nutrition; v. 36, n. 4, p. 1149-1157, AUG 2017.
• Web of Science Citations: 1

Abstract

Tissues that require a great supply of nutrients and possess high metabolic demands, such as lympho-hemopoietics tissues, are the first to be affected by protein malnutrition (PM). Thus, PM directly affects hemopoiesis and the production and function of immune cells. Consequently, malnourished individuals are more susceptible to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are important in the formation of lympho-hemopoietic stroma. Since an adequate supply of nutrients is essential to sustain stroma formation, which is mainly constituted of MSCs and differentiated cells originated from them, this study investigated whether PM would influence some biological and immunomodulatory aspects of MSCs. Two-month-old Balb/c mice were divided into control and malnourished groups receiving normoproteic or hypoproteic diets, respectively (12% and 2% of protein) for 28 days. MSCs obtained from control (MSCct) and malnourished (MSCmaln) animals were characterized. In addition, the proliferation rate and cell cycle protein expression were determined, but no differences in these parameters were observed. In order to evaluate whether PM affects the immunomodulatory properties of MSCs, the expression of WO and STAT-3, and the production of IL-1 alpha, IL-1 beta, IL-6, IL-10, TGF-beta and TNF-alpha by MSCs were assessed. MSCmaln expressed lower levels of NF-kappa B and the production of IL-1 beta, IL-6 and TGF-beta was significantly influenced by PM. Furthermore, MSCct and MSCmaln culture supernatants affected lymphocyte and macrophage proliferation. However, MSCmaln did not reduce the production of IFN-gamma nor stimulate the production of IL-10 in lymphocytes in the same manner as observed in MSCct. Overall, this study implied that PM modifies immunosuppressive properties of MSCs. (C) 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. (AU)

• FAPESP's process: 14/06872-2 - Evaluation of hematopoietic regulatory aspects in protein malnutrition: the role of bone marrow endothelial-like cells derived from mesenchymal stem cells
• Grantee: Ricardo Ambrósio Fock
• Support Opportunities: Regular Research Grants