Effects of protein malnutrition on haematopoietic regulatory activity of bone marrow mesenchymal stem cells.

Abstract Protein malnutrition causes anaemia and leukopenia as it reduces haematopoietic precursors and impairs the production of mediators that regulate haematopoiesis. Haematopoiesis occurs in distinct bone marrow niches that modulate the processes of differentiation, proliferation and self-renewal of haematopoietic stem cells (HSCs). Mesenchymal stem cells (MSCs) contribute to the biochemical composition of bone marrow niches by the secretion of several growth factors and cytokines, and they play an important role in the regulation of HSCs and haematopoietic progenitors. In this study, we investigated the effect of protein malnutrition on the haematopoietic regulatory function of MSCs. C57BL/6NTaq mice were divided into control and protein malnutrition groups, which received, respectively, a normal protein diet (12% casein) and a low protein diet (2% casein). The results showed that protein malnutrition altered the synthesis of SCF, TFG-β, Angpt-1, CXCL-12, and G-CSF by MSCs. Additionally, MSCs from the protein malnutrition group were not able to maintain the lymphoid, granulocytic and megakaryocytic-erythroid differentiation capacity compared to the MSCs of the control group. In this way, the comprehension of the role of MSCs on the regulation of the haematopoietic cells, in protein malnutrition states, is for the first time showed. Therefore, we infer that haematopoietic alterations caused by protein malnutrition are due to multifactorial alterations and, at least in part, the MSCs’ contribution to haematological impairment.