The Effect of Methyl-β-cyclodextrin on Apoptosis, Proliferative Activity, and Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells of Horses Suffering from Metabolic Syndrome (EMS).

Joanna Szydlarska,Krzysztof Marycz,Christine Weiss

doi:10.3390/molecules23020287

Abstract

Methyl-β-cyclodextrin (MβCD) is a cyclic oligosaccharide, commonly used as a pharmacological agent to deplete membrane cholesterol. In this study, we examined the effect of MβCD on adipose-derived mesenchymal stromal cells (ASCs) isolated form healthy horses (ASCCTRL) and from horses suffering from metabolic syndrome (ASCEMS). We investigated the changes in the mRNA levels of the glucose transporter 4 (GLUT4) and found that MβCD application may lead to a significant improvement in glucose transport in ASCEMS. We also showed that MβCD treatment affected GLUT4 upregulation in an insulin-independent manner via an NO-dependent signaling pathway. Furthermore, the analysis of superoxide dismutase activity (SOD) and reactive oxygen species (ROS) levels showed that MβCD treatment was associated with an increased antioxidant capacity in ASCEMS. Moreover, we indicated that methyl-β-cyclodextrin treatment did not cause a dysfunction of the endoplasmic reticulum and lysosomes. Thereby, we propose the possibility of improving the functionality of ASCEMS by increasing their metabolic stability.

Highlights

Nowadays, equine metabolic syndrome (EMS) has become one of the most common metabolic disorders in horses and has been steadily growing in the recent years
adipose-derived mesenchymal stromal cells (ASCs) determined by measuring the reduction of resazurin to resorufin in the first, third, and fifth daywas of methyl-β-cyclodextrin treatment
We examined the effect of methyl-β-cyclodextrin on the biological functions of adipose-derived mesenchymal stromal cells of equine metabolic syndrome-affected horses (ASCEMS)

Summary

Introduction

Equine metabolic syndrome (EMS) has become one of the most common metabolic disorders in horses and has been steadily growing in the recent years. The disturbance of the metabolic balance is most likely due to the an improper, high-calorie diet, rich in sugar and concentrates, combined with limited exercise [1]. Mesenchymal stromal cells (MSCs) are a population of multipotent cells, characterized by a high proliferative and differentiation potential, a great capacity for self-renewal, and the ability to modulate the immune response by secreting cytokines, antiapoptotic factors, and growth factors via membrane-derived vesicle (MVs) shedding [5]. Recent data indicates MSCs cytophysiological impairment in the course of metabolic diseases [8,9] such as obesity and metabolic syndromes. Our laboratory’s previous studies demonstrated that EMS is closely

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