title: Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner.
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 isolated 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 endothelial cells (EC), but MSC-derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL-6 and TGFβ1 signalling 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 immunoprotective. 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 immunoprotective phenotype. Stem Cells 2017;35:1636-1646.
authors.affiliation: Institute for Cardiovascular Sciences, College of Medical and Dental Sciences.
authors.forename: Hafsa
authors.initials: H
authors.lastname: Munir
authors.affiliation: Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Lewis S C
authors.initials: LSC
authors.lastname: Ward
authors.affiliation: Institute for Cardiovascular Sciences, College of Medical and Dental Sciences.
authors.forename: Lozan
authors.initials: L
authors.lastname: Sheriff
authors.affiliation: Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kemble
authors.affiliation: Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Saba
authors.initials: S
authors.lastname: Nayar
authors.affiliation: Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Barone
authors.affiliation: Institute for Cardiovascular Sciences, College of Medical and Dental Sciences.
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Nash
authors.affiliation: Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Helen M
authors.identifier: 0000-0002-5950-8840
authors.initials: HM
authors.lastname: McGettrick
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D018920:Coculture Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D056747:Immunomodulation; D007165:Immunosuppression Therapy; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology*; D009928:Organ Specificity; D020543:Proteome / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D020543:Proteome; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1
keywords: Adipocytes; Endothelial cells; Inflammation; Mesenchymal stem cells; Neutrophils; Tissue-specific