Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging

Abstract

Currently, equine metabolic syndrome (EMS), an endocrine disease linked to insulin resistance, affects an increasing number of horses. However, little is known about the effect of EMS on mesenchymal stem cells that reside in adipose tissue (ASC). Thus it is crucial to evaluate the viability and growth kinetics of these cells, particularly in terms of their application in regenerative medicine. In this study, we investigated the proliferative capacity, morphological features, and accumulation of oxidative stress factors in mesenchymal stem cells isolated from healthy animals (ASCN) and horses suffering from EMS (ASCEMS). ASCEMS displayed senescent phenotype associated with β-galactosidase accumulation, enlarged cell bodies and nuclei, increased apoptosis, and reduced heterochromatin architecture. Moreover, we observed increased amounts of nitric oxide (NO) and reactive oxygen species (ROS) in these cells, accompanied by reduced superoxide dismutase (SOD) activity. We also found in ASCEMS an elevated number of impaired mitochondria, characterized by membrane raptures, disarrayed cristae, and vacuole formation. Our results suggest that the toxic compounds, accumulating in the mitochondria under oxidative stress, lead to alternations in their morphology and may be partially responsible for the senescent phenotype and decreased proliferation potential of ASCEMS.

Macroautophagy and Selective Mitophagy Ameliorate Chondrogenic Differentiation Potential in Adipose Stem Cells of Equine Metabolic Syndrome: New Findings in the Field of Progenitor Cells Differentiation

“…What is more, as mentioned above mir plays crucial role in switching on proinflammatory genes expression. It stands in good agreement and fulfilled our previous findings, where we showed that native ASC EMS were characterized by upregulation of p21, p53, and cas-9 as well as BAX expression in comparison to healthy ASC [10]. …”

“…However, EMS as a serious endocrine disorder, which is steadily growing, has unquestioned impact on ASCs cytophysiology [10]. As it was previously demonstrated ASC of EMS horses (ASC EMS ) are marked by excessive molecular aging, decreased viability, displayed senescence associated features, and abundantly accumulated oxidative stress factors [10]. Hence, we were interested whether ASC EMS are characterized by impaired chondrogenic differentiation potential, since those cells are commonly used for the regenerative medicine purposes.…”

“…It is tempting to speculate that similar, paradox, mechanism is switched on in EMS horses, standing as an adaptation to help animals maintain their metabolic help. Moreover, feeding mice on high-fat diet accelerated FGF21 beneficial effect; thus activating FGF21 by deteriorated mitochondria may be indeed the protective mechanism in individuals suffering from diabetes and metabolic syndrome, especially the fact that mitochondrial dysfunction in both of these diseases was proved in many studies [10, 31–33]. …”

“…However, it seems that the autophagy process is not always associated with autolysosome formation and does not necessarily lead to apoptosis. The hypothesis proposed is that EMS conditions might temporarily induce autophagy in stem progenitor cells, allowing them to keep physiological functions and survive [10]. In the course of the autophagy several genes and their products, called ATG and atg, respectively, are involved in its regulation.…”

Combination of resveratrol and 5‐azacytydine improves osteogenesis of metabolic syndrome mesenchymal stem cells

“…Previous studies have shown that ASCs isolated from EMS horses (ASC EMS ) suffered from reduced proliferative activity, progressive apoptosis, ageing and senescence, which eventually impaired their multipotency and osteogenic differentiation potential. [27][28][29] It was shown that ASCs EMS exhibited reduced secretion of extracellular microvesicels (ExMVs) rich in bone morphogenetic protein 2 (BMP-2), collagen type II (COll-2) or osteocalcin (OCN)-all fundamental for ontogenesis. Deterioration of differentiation potential was caused by dysfunction of mitochondrial metabolism and dynamics.…”