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.
Highlights
Type 2 diabetes mellitus (T2DM) is reaching epidemic proportions worldwide
Scale bar = 100 lm. (B) Quantification of the tubular-like structures formed by human umbilical vein endothelial cells (HUVECs) in conditioned media (CM)-Lean control (LEAN), CM-Zucker diabetic fatty rats (ZDF), FM or NCM cultured on Matrigel
Despite the fact that bone marrow mesenchymal stem cell (BMMSC)-derived paracrine factors were reported to be largely involved in neovascularization and tissue repair, the impact of type 2 diabetes mellitus (T2DM) on the BMMSC secretome and its effects on angiogenesis are still unknown [16, 17]
Summary
The persistent hyperglycaemic milieu in T2DM is associated with macro- and micro-vascular complications affecting the heart, blood vessels, eyes, kidney and nerves, and the wound-healing process in diabetic patients [1,2,3]. Most of the T2DM pathological complications are associated with impaired vascularization and/or aberrant angiogenesis. Excessive and abnormal angiogenesis plays a pivotal role in diabetic retinopathy and nephropathy [4, 5], whereas deficient angiogenesis contributes to impaired wound healing and coronary collateral vessel development [1, 3, 6]. The mechanism(s) behind the abnormal angiogenesis balance in diabetic patients is still poorly understood. Scientific research has provided evidence that the dysfunction of different types of cells, including endothelial, peripheral blood and a 2016 The Authors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
