title: Type 2 diabetes alters mesenchymal stem cell secretome composition and angiogenic properties.
abstract: This study aimed at characterizing the impact of type 2 diabetes mellitus (T2DM) on the bone marrow mesenchymal stem cell (BMMSC) secretome and angiogenic properties. BMMSCs from Zucker diabetic fatty rats (ZDF) (a T2DM model) and Zucker LEAN littermates (control) were cultured. The supernatant conditioned media (CM) from BMMSCs of diabetic and control rats were collected and analysed. Compared to results obtained using CM from LEAN-BMMSCs, the bioactive content of ZDF-BMMSC CM (i) differently affects endothelial cell (HUVEC) functions in vitro by inducing increased (3.5-fold; P < 0.01) formation of tubule-like structures and migration of these cells (3-fold; P < 0.001), as well as promotes improved vascular formation in vivo, and (ii) contains different levels of angiogenic factors (e.g. IGF1) and mediators, such as OSTP, CATD, FMOD LTBP1 and LTBP2, which are involved in angiogenesis and/or extracellular matrix composition. Addition of neutralizing antibodies against IGF-1, LTBP1 or LTBP2 in the CM of BMMSCs from diabetic rats decreased its stimulatory effect on HUVEC migration by approximately 60%, 40% or 40%, respectively. These results demonstrate that BMMSCs from T2DM rats have a unique secretome with distinct angiogenic properties and provide new insights into the role of BMMSCs in aberrant angiogenesis in the diabetic milieu.
authors.affiliation: Laboratory of Bioingénierie et Biomécanique Ostéo-articulaires-UMR CNRS 7052 Paris 7-Denis Diderot University, Sorbonne Paris Cite, Paris, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ribot
authors.affiliation: Laboratory of Bioingénierie et Biomécanique Ostéo-articulaires-UMR CNRS 7052 Paris 7-Denis Diderot University, Sorbonne Paris Cite, Paris, France.
authors.forename: Guavri
authors.initials: G
authors.lastname: Caliaperoumal
authors.affiliation: Laboratory of Bioingénierie et Biomécanique Ostéo-articulaires-UMR CNRS 7052 Paris 7-Denis Diderot University, Sorbonne Paris Cite, Paris, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Paquet
authors.affiliation: INSERM, UMR 1140, Université Paris Descartes, Sorbonne Paris Cite, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Boisson-Vidal
authors.affiliation: Laboratory of Bioingénierie et Biomécanique Ostéo-articulaires-UMR CNRS 7052 Paris 7-Denis Diderot University, Sorbonne Paris Cite, Paris, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Petite
authors.affiliation: Laboratory of Bioingénierie et Biomécanique Ostéo-articulaires-UMR CNRS 7052 Paris 7-Denis Diderot University, Sorbonne Paris Cite, Paris, France.|Department of Periodontology, Service of Odontology, Pitié Salpêtrière Hospital et Hôtel-Dieu Hospital AP-HP, U.F.R. of Odontology Paris 7-Denis Diderot University, Sorbonne Paris Cite, Paris, France.
authors.forename: Fani
authors.identifier: 0000-0002-0065-2127
authors.initials: F
authors.lastname: Anagnostou
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011924:Rats, Zucker; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D020543:Proteome; D017382:Reactive Oxygen Species; D007334:Insulin-Like Growth Factor I
keywords: MSCs; angiogenesis; diabetes type 2; endothelial cells; secretome