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.
Highlights
Nowadays, the obesity is an increasing problem in both human and veterinary medicine [1]
In order to confirm the multipotent character of isolated EqASCs, we performed immunohistochemical staining and multipotency assay
EqASCs were able to differentiate into osteogenic, chondrogenic, and adipogenic lineages, which was confirmed by means of appropriate immunohistochemistry (Figure 2)
Summary
The obesity is an increasing problem in both human and veterinary medicine [1]. The later clinical sign of EMS, that is, “local adiposity,” seems to be extremely important in the context of local inflammation and accelerated aging of adipose tissue taking place inside it. This environment becomes simultaneously the direct tissue milieu for mesenchymal stem cells that reside within adipose tissue. The action of proinflammatory cytokines, including a broad range of adipokines, such as leptin, resistin, adiponectin, visfatin, and apelin, which are abundantly present in the adipose tissue of EMS horses, cannot remain without physiological relevance for equine adipose-derived mesenchymal stromal stem cells
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