Evaluation of Oxidative Stress and Mitophagy during Adipogenic Differentiation of Adipose-Derived Stem Cells Isolated from Equine Metabolic Syndrome (EMS) Horses.

Krzysztof Marycz,Christine Weiss,Agnieszka Śmieszek,Katarzyna Kornicka

doi:10.1155/2018/5340756

Abstract

Mesenchymal stem cells (MSCs) are frequently used in both human and veterinary medicine because their unique properties, such as modulating the immune response and differentiating into multiple lineages, make them a valuable tool in cell-based therapies. However, many studies have indicated the age-, lifestyle-, and disease-related deterioration of MSC regenerative characteristics. However, it still needs to be elucidated how the patient's health status affects the effectiveness of MSC differentiation. In the present study, we isolated mesenchymal stem cells from adipose tissue (adipose-derived mesenchymal stem cells (ASCs)) from horses diagnosed with equine metabolic syndrome (EMS), a common metabolic disorder characterized by pathological obesity and insulin resistance. We investigated the metabolic status of isolated cells during adipogenic differentiation using multiple research methods, such as flow cytometry, PCR, immunofluorescence, or transmission and confocal microscopy. The results indicated the impaired differentiation potential of ASCEMS. Excessive ROS accumulation and ER stress are most likely the major factors limiting the multipotency of these cells. However, we observed autophagic flux during differentiation as a protective mechanism that allows cells to maintain homeostasis and remove dysfunctional mitochondria.

Highlights

Mesenchymal stem cells (MSCs) can be isolated from multiple sources, including bone marrow and adipose tissue [1, 2]
MSCs from adipose tissue (adipose-derived mesenchymal stem cells (ASCs)) can be obtained with a minimal invasive procedure, much attention has been paid to their clinical application [3,4,5]
The accumulation of mineralized matrix was proved by Alizarin Red, while the formation of proteoglycans was proved by Safranin O dye

Summary

Introduction

Mesenchymal stem cells (MSCs) can be isolated from multiple sources, including bone marrow and adipose tissue [1, 2]. MSCs from adipose tissue (adipose-derived mesenchymal stem cells (ASCs)) can be obtained with a minimal invasive procedure, much attention has been paid to their clinical application [3,4,5]. ASCs are multipotent cells capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. They are characterized by the presence of specific surface antigens, including CD73, CD90, and CD105, while they lack expression of CD45 [6]. The proregenerative properties of ASCs are mostly based on the secretion and intercellular transfer of extracellular membrane-derived vesicles (ExMVs), carrying growth factors including fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) [4, 9]. The knowledge of the mechanisms responsible for survival and differentiation of ASCs is absolutely necessary to develop beneficial and innovative therapeutic strategies

Methods

Results

Conclusion