The Hematopoietic Growth Factor “Erythropoietin” Enhances the Therapeutic Effect of Mesenchymal Stem Cells in Alzheimer’s Disease

Abstract

Alzheimer's disease is a neurodegenerative disorder clinically characterized by cognitive dysfunction and by deposition of amyloid plaques, neurofibrillary tangles in the brain. The study investigated the therapeutic effect of combined mesenchymal stem cells and erythropoietin on Alzheimer's disease. Five groups of mice were used: control group, Alzheimer's disease was induced in four groups by a single intraperitoneal injection of 0.8 mg kg(-1) lipopolysaccharide and divided as follows: Alzheimer's disease group, mesenchymal stem cells treated group by injecting mesenchymal stem cells into the tail vein (2 x 10(6) cells), erythropoietin treated group (40 microg kg(-1) b.wt.) injected intraperitoneally 3 times/week for 5 weeks and mesenchymal stem cells and erythropoietin treated group. Locomotor activity and memory were tested using open field and Y-maze. Histological, histochemical, immunohistochemical studies, morphometric measurements were examined in brain sections of all groups. Choline transferase activity, brain derived neurotrophic factor expression and mitochondrial swellings were assessed in cerebral specimens. Lipopolysaccharide decreased locomotor activity, memory, choline transferase activity and brain derived neurotrophic factor. It increased mitochondrial swelling, apoptotic index and amyloid deposition. Combined mesenchymal stem cells and erythropoietin markedly improved all these parameters. This study proved the effective role of mesenchymal stem cells in relieving Alzheimer's disease symptoms and manifestations; it highlighted the important role of erythropoietin in the treatment of Alzheimer's disease.

The Effect of Thymoquinone, α7 Receptor Agonist and α7 Receptor Allosteric Modulator on the Cerebral Cortex in Experimentally Induced Alzheimer's Disease in Relation to MSCs Activation

“…Increase in the mean area of plaques was found in group 2. In accordance, Aβ aggregation has been identified as one of the major causes of neurodegenerative processes in AD (18) and were demonstrated in cerebral sections of AD induced in mice (19). …”

Neuroprotective effects of erythropoietin on Alzheimer’s dementia model in rats

“…This finding is in accordance with previous studies reporting increased ChAT activity induced by rhEPO in STZ-and lipopolysaccharide-induced sporadic-AD animal models. 25,26 Neuroinflammation is also an important component in the pathogenesis and progression of AD. TNF-α is the major cytokine synthesized by activated microglia and neurons and initiating the inflammatory cascade.…”

“…27 Interestingly, EPO promotes mesenchymal stem cells to differentiate into cholinergic neurons, resulting in increased ChAT activity and ACh level in lipopolysaccharide-treated mice. 25 Both EPO and its receptor (EPOR) are expressed by glial cells, neuronal pregenitor cells, neurons and cerebrovascular endothelium in rodent and human brains, and show high immunopositivity in the frontal cortex and hippocampus. 30 EPOR is upregulated in the brain upon injury or neurodegenerative conditions, such as in the temporal cortex and hippocampus of patients with mild cognitive impairment or AD, which may be because of the increased cell requirements for this hormone.…”

Cell-based therapy in Alzheimer's disease: Current knowledge and perspective

“…MSCs increase hippocampal neurogenesis, neuronal differentiation, and the formation of neurites in AD animal's model [33][34][35] .…”