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Type 2 diabetes alters mesenchymal stem cell secretome composition and angiogenic properties

Authors
  • Ribot, Jonathan
  • Caliaperoumal, Guavri
  • Paquet, Joseph
  • Boisson-Vidal, Catherine
  • Petite, Herve
  • Fani Anagnostou
Type
Published Article
Journal
Journal of Cellular and Molecular Medicine
Publisher
Wiley
Publication Date
Sep 26, 2016
Volume
21
Issue
2
Pages
349–363
Identifiers
DOI: 10.1111/jcmm.12969
PMID: 27641937
PMCID: PMC5264143
OAI: oai:HAL:hal-01492611v1
Source
USPC - SET - SVS
Keywords
License
Green
External links

Abstract

This study aimed at characterizing the impact of type 2 diabetes mellitus (T2DM) on the bone marrow mesenchymal stem cell (BMMSC) secre-tome 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.

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