Helen McGettrick
University of Birmingham, UK
Title: Adipogenic differentiation of MSC alters their immunomodulatory properties in a tissue-specific manner
Biography
Biography: Helen McGettrick
Abstract
Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage-induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC from bone marrow or adipose tissue on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue. Bone marrow derived MSC were immunosuppressive, inhibiting neutrophil recruitment to TNFα-treated EC, but MSC derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL-6 and TGFβ1 signaling appeared critical for the loss of the immunosuppressive phenotype. In contrast, native stromal cells, adipocytes derived from them and mature adipocytes from adipose tissue were all immuno-protective. Thus, disruption of normal tissue stroma homeostasis, as occurs in chronic inflammatory diseases, might drive abnormal adipogenesis which adversely influences the behavior of MSC and contributes to pathogenic recruitment of leukocytes. Interestingly, stromal cells programmed in native fat tissue retain an immuno-protective phenotype.