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Stem cell-based regenerative therapies hold great promises to treat a wide spectrum of diseases. However, stem cell engraftment and survival are still challenging due to an unfavorable transplantation environment. Advanced glycation end-products (AGEs) can contribute to the generation of these harmful conditions. AGEs are a heterogeneous group of glycated products, nonenzymatically formed when proteins and/or lipids become glycated and oxidized. Our typical Western diet as well as cigarettes contain high AGEs content. AGEs are also endogenously formed in our body and accumulate with senescence and in pathological situations. Whether AGEs have an impact on stem cell viability in regenerative medicine remains unclear, and research on the effect of AGEs on stem cell proliferation and apoptosis is still ongoing. Therefore, this systematic review provides a clear overview of the effects of glycated proteins on cell viability in various types of primary isolated stem cells used in regenerative medicine. Figures were created using images from Servier Medical Art Commons Attribution 3.0 Unported License (http://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License. This work was supported by a Bijzonder onderzoeksfonds (BOF) grant from Hasselt University (grant number: 16NI05BOF). HB benefits from an aspirant PhD mandate (grant number: 1154120N) of the `Research Foundation-Flanders' (fonds voor wetenschappelijk onderzoek (FWO)). PG is also supported by the FWO (grant numbers: 12U7718N and 1502120N). Bito, V (corresponding author), Hasselt Univ, Biomed BIOMED Res Inst, Agoralaan Bldg C, B-3590 Diepenbeek, Belgium. virginie.bito@uhasselt.be

Background. Several studies have shown that advanced glycation end products (AGEs) are associated with adverse cardiac outcome. In that context, growing evidence show that high molecular weight AGEs (HMW-AGEs) play a role as important as the well characterized low molecular weight AGEs (e.g. pentosidine and carboxymethyllysine), chronically but also possibly acutely. Objective. In this study, we investigated whether HMW-AGEs acutely alter Ca2+ homeostasis in cardiomyocytes. Methodology. Single cardiomyocytes from the left ventricle of adult male rats were obtained by enzymatic dissociation. Ionic currents were evaluated during whole cell patch-clamp in the presence or absence of HMW-AGEs (200 µg/ml) and normalized to cell capacitance. Data are expressed as mean ± SEM. Results. After 4 minutes HMW-AGEs application, peak ICaL measured at +10 mV significantly decreased (-5.2±0.6 pA/pF vs -7.8±1.1 pA/pF at baseline, ncells =10, p, Journal of International Society of Antioxidants in Nutrition & Health, Vol 3, No 2 (2016): Journal of ISANH Volume 3: Special Issue for Maillard Reaction & Glycation

Purpose: Left ventricular (LV) twist and untwist rate (UR) are known to be strongly related to LV systolic and diastolic function, respectively. Although these parameters are emerging as important tools to evaluate LV function, yet their assessment and physiological significance in small animals remain challenging. The study was designed to investigate how twist and UR, measured by speckle tracking imaging (STI), relate to LV function and extent of fibrosis in a rat model of chronic myocardial infarction (MI). Methods: 23 Sprague-Dawley rats were subjected to LAD ligation (MI; n=14) or sham surgery (SHAM; n=9). 2D echocardiography at baseline (BL), day 1, day 3 and 2 months post-surgery was used to calculate LV dimensions, volumes (EDV, ESV) and global functional parameters. STI was applied to measure circumferential strain (Scirc), twist and UR. LV fibrosis was estimated from Sirius Red staining at day 1, day 3 and 2 months post-surgery. Results: Progressive cardiac failure evaluated during 2 months was characterized by a gradual increase in EDV and ESV respectively (0.2±0.04 mL to 0.8±0.2mL, and 0.04±0.02mL to 0.5±0.1 from BL to 2 months post-surgery, p

Schmidtea mediterranea beschikt over een enorme populatie totipotente stamcellen, neoblasten genoemd. Deze cellen omvatten 30% van het totaal aantal cellen in dit organisme en het zijn bovendien de enige delende cellen in S. mediterranea. Aangezien vele kankers ontstaan door een defect regulatiemechanisme van de (stam)celdeling, is het een zeer geschikt modelorganisme voor het bestuderen van carcinogene processen. Eerder werd aangetoond dat een blootstelling aan cadmium (Cd) en hexavalent chroom (Cr(VI)) de stamcelproliferatie verhoogt in deze platworm. Het is echter nog niet geweten of deze metaal-geïnduceerde stamcelproliferatie gelinkt kan worden aan schade (kanker) of aan een herstelmechanisme. De onderliggende mechanismen van Cd- en Cr(VI)-geïnduceerde stamcelproliferatie kan worden onderzocht via een proteoomscreening. Het doel van mijn thesis kadert binnen de onderzoeksvraag die deze stress-geïnduceerde (stam)celproliferatie probeert te karakteriseren, waarbij ik de condities vo

Chronically increased levels of high molecular weight advanced glycation end products (HMW-AGEs) are known to induce cardiovascular dysfunction. Whether an acute increase in HMW-AGE levels affects vascular function remains unknown. In this study, we examined whether acute exposure to HMW-AGEs disturbs aortic vasomotor function. Aortae were obtained from healthy male rats and were acutely pre-treated with HMW-AGEs in organ baths. Aortic relaxation responses to cumulative doses of acetylcholine (ACh), in the presence or absence of superoxide dismutase (SOD), were measured after precontraction with phenylephrine (PE). Furthermore, levels of 3-nitrotyrosine were evaluated on aortic paraffine sections. In our study, we show that acute exposure to HMW-AGEs significantly decreases the aortic relaxation response to ACh. SOD pre-treatment prevents acute HMW-AGEs-induced impairment by limiting superoxide formation. In conclusion, our data demonstrate that acute exposure to HMW-AGEs causes adverse vascular remodelling, characterised by disturbed vasomotor function due to increased oxidative stress. These results create opportunities for future research regarding the acute role of HMW-AGEs in cardiovascular dysfunction. This research was funded by a Bijzonder onderzoeksfonds (BOF) grant from Hasselt University, grant number: 16NI05BOF. We thank Jeanine Santermans for embedding the tissues in paraffin. The authors also thank Petra Bex for her skilful technical assistance. The graphical abstract was created using images from Biorender and ServierMedical Art Commons Attribution 3.0 Unported License (http: //smart.servier.com, accessed on 2 September 2022). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License.

Cardiovascular diseases (CVD) are the number one cause of death globally, affecting many people in low- and middle-income countries. Recent studies suggested that high-molecular-weight advanced glycation end-products (HMW-AGEs) contribute to CVD development. Despite the lack of scientific knowledge, plant extracts of Origanum compactum (O. compactum) are commonly used by the Moroccan population to treat diseases like diabetes and hypertension. In this study, we investigated the acute effects of O. compactum on the cardiovascular system and whether it can prevent the harmful effects caused by HMW-AGEs. To investigate this, cardiomyocytes were isolated from healthy Sprague-Dawley rats by enzymatic dissociation through retrograde perfusion of the aorta. Cardiomyocytes were used as control or pre-incubated for 30 minutes with O. compactum (1, 5, 10 or 100 μg/mL). Unloaded cell shortening was measured before and after application of HMW-AGEs (200 μg/mL) for 7 minutes. Whole-cell patch-clamp was performed to measure the electrophysiological properties. Additionally, the effect of O. compactum was assessed on the contraction and relaxation responses of aortic rings to phenylephrine (PE), acetylcholine (ACh), and sodium nitroprusside (SNP). Our study demonstrates that O. compactum increases cardiomyocyte unloaded cell shortening and contributes to arterial stiffness, promoting hypertension.

Advanced glycation end products (AGEs) are compounds formed by irreversible glycation of proteins. Our research group has recently demonstrated that high-molecular-weight AGEs (HMW-AGEs) impair cardiac function in healthy rats. This project aims to examine the effect of HMW-AGEs on vascular function and to investigate ultrastructural abnormalities in cardiomyocytes. Therefore, male Sprague Dawley rats were daily intraperitoneally injected with either HMW-AGEs or a control solution for six weeks. Plasma AGEs levels and cardiac hemodynamic parameters were evaluated to validate this animal model. The relaxation responses to cumulative doses of acetylcholine (ACh) or sodium nitroprusside (SNP) were assessed in isolated rat aortic rings. Microscopy was performed to examine the ultrastructural cardiomyocyte organization. HMW-AGEs injections in rats significantly increased plasma AGEs levels and cardiac pressure. The vasorelaxation response to ACh but not to SNP was decreased in HMW-AGEs animals, indicating impaired endothelium-dependent relaxation. Interestingly, superoxide dismutase restored relaxation in aortic rings from HMW-AGEs animals, which indicates that HMW-AGEs disturb vascular function through superoxide formation. In addition, we show that HMW-AGEs cause ultrastructural remodeling in cardiomyocytes, characterized by an increase in cytoplasmic fraction and a reduction of mitochondrial area and number in cardiomyocytes. This research provides more insight into the role of HMW-AGEs in cardiovascular disease.