Development of novel human in vitro vascularized adipose tissue model with functional macrophages
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ORIGINAL ARTICLE
Development of novel human in vitro vascularized adipose tissue model with functional macrophages Outi Huttala . Jertta-Riina Sarkanen . Marika Mannerstro¨m . Tarja Toimela . Tuula Heinonen . Timo Ylikomi
Received: 7 March 2020 / Accepted: 4 June 2020 Ó The Author(s) 2020
Abstract Inflammation has been proven significant factor in development of type 2 diabetes. So far, most of the adipose tissue related research has been performed in animals, mainly rodent models. The relevance of translation of animal results to humans is questionable. However, in vitro model with relevant human cell source, such as human adipose tissue stromal cells (hASC), can be developed and should be utilized for human adipose tissue research. We developed in vitro models of human adipose tissue utilizing hASC, endothelial cells and monocytes/macrophages. By isolating endothelial cells and macrophages from same adipose tissue as hASC, we were able to provide method for constructing personalized models of adipose tissue. With these models, we studied the effect of macrophages on adipogenesis and protein secretion, with and without vasculature. The models were analyzed for immunocytochemical markers, cell number, triglyceride accumulation and protein secretion. We found that lipid accumulation was greater in adipocytes in the presence of macrophages. Interferon gamma increased this difference between adipocyte culture and Adipocyte– O. Huttala M. Mannerstro¨m T. Toimela T. Heinonen FICAM, Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland O. Huttala (&) J.-R. Sarkanen T. Ylikomi Cell Biology, Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland e-mail: [email protected]
Macrophage co-culture. Protein secretion was affected more by macrophages when vasculature was not present compared to the mild effect when vasculature was present. The vascularized adipose model with macrophages is valuable tool for human adipose tissue research, especially for the personalized medicine approaches; for choosing the right treatments and for studying rare medical conditions. Keywords hASC Adipose tissue derived endothelial cells Interferon gamma Adipogenesis In vitro model development Adipose tissue derived macrophages Abbreviations AMM Adipocyte–Macrophage Model AMMI Adipocyte–Macrophage Model with IFNc ATE Adipose tissue extract G-CSF Granulocyte-colony stimulating factor GMGranulocyte–macrophage colonyCSF stimulating factor hASC Human adipose stromal cells HUVEC Human umbilical vein endothelial cells IFNc Interferon gamma IGF Insulin-like growth factor 1 IL-1a Interleukin 1a IL-6 Interleukin 6 IL-8 Interleukin 8 IP-10 Interferon gamma-induced protein 10/CXCL10
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Cytotechnology
LDL PAI RT SFM TGFb TNFa VATMI
Low density lipoprotein Plasminogen activator inhibitor 1 Room temperature Serum free medium Transforming growth factor b Tumor necrosis factor a Vascularized Adipose Tissue model with Macrophages w
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