Transplantation of bone marrow mesenchymal stem cells decreases oxidative stress, apoptosis, and hippocampal damage in brain of a spontaneous stroke model

Abstract

Stroke is the most common cause of motor disabilities and is a major cause of mortality worldwide. Adult stem cells have been shown to be effective against neuronal degeneration through mechanisms that include both the recovery of neurotransmitter activity and a decrease in apoptosis and oxidative stress. We chose the lineage stroke-prone spontaneously hypertensive rat (SHRSP) as a model for stem cell therapy. SHRSP rats can develop such severe hypertension that they generally suffer a stroke at approximately 1 year of age. The aim of this study was to evaluate whether mesenchymal stem cells (MSCs) decrease apoptotic death and oxidative stress in existing SHRSP brain tissue. The results of qRT-PCR assays showed higher levels of the antiapoptotic Bcl-2 gene in the MSC-treated animals, compared with untreated. Our study also showed that superoxide, apoptotic cells, and by-products of lipid peroxidation decreased in MSC-treated SHRSP to levels similar those found in the animal controls, Wistar Kyoto rats. In addition, we saw a repair of morphological damage at the hippocampal region after MSC transplantation. These data suggest that MSCs have neuroprotective and antioxidant potential in stroke-prone spontaneously hypertensive rats.

Stroke and Mesenchimal Stromal Cells: Mechanisms of Neuroprotection and Future Prospects

“…Recently many evidences have shown the efficacy of MSCs treatment both in in vitro [11] and in vivo models of ischemia [12]. Treatment, in vitro, with MSCs protected a neuronal cell line against oxygen-glucose deprivation damage through the secretion of vascular endothelial growth factor and interleukin-6 (IL-6).…”

“…It has been also demonstrated, in vivo, that subcutaneous administration of MSCs increased survival in stroke-prone spontaneously hypertensive rats, with increased levels of the antiapoptotic gene Bcl-2 and decreased superoxide production in the ischemic area [12]. MSCs neuroprotective effect could act either on apoptosis and autophagy:…”

“…This stress causes an increase in the p38 phosphorylation and, consequently, an augmented release of fibroblast growth factor 2 and bone morphogenetic protein 2. These two growth factors activated the MEK/ERK cascade and Smad 1/5/8, respectively, bringing to an increased neurite growth [14].It has been also demonstrated, in vivo, that subcutaneous administration of MSCs increased survival in stroke-prone spontaneously hypertensive rats, with increased levels of the antiapoptotic gene Bcl-2 and decreased superoxide production in the ischemic area [12]. MSCs neuroprotective effect could act either on apoptosis and autophagy:…”

“…Although bone marrow was the first source to be identified [8], MSCs have been successfully isolated from adipose tissue, pancreas, liver, skeletal muscle, dermis, synovial membrane, and trabecular bone [9]. In vitroexpanded MSCs also have remarkable properties due to their capacity to produce a variety of growth factors, cytokines, chemokines and proteases that likely could play immunomodulatory roles after their migration into inflamed regions [10].Recently many evidences have shown the efficacy of MSCs treatment both in in vitro [11] and in vivo models of ischemia [12]. Treatment, in vitro, with MSCs protected a neuronal cell line against oxygen-glucose deprivation damage through the secretion of vascular endothelial growth factor and interleukin-6 (IL-6).…”

Mesenchymal stem cells seem too good to believe!

“…MSCs have been injected into stroke-prone spontaneously hypertensive rats (SHR). The authors of that report claimed that MSCs had antioxidant and anti-apoptotic effects as well as the ability to repair hippocampal damage in SHR [4]. However, a reduction in blood pressure was not reported.…”