Mesenchymal stem cells act as stimulators of neurogenesis and synaptic function in a rat model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is one of the most common NDs leading to cognitive dysfunctions and dementia which are progressively worsen with age. Cell therapy is currently of particular interest in treatment of neurodegenerative disease (ND) such as AD. However, the effective treatment for AD is yet to be found. OBJECTIVE: In this study, the possible roles of human umbilical mesnchymal stromal cord (hUMSCs) and adipose mesenchymal stem cells (hAD-MSCs) in neurogenesis and synaptic function were investigated using a ß-amyloid 1-42 (ß A42)-induced AD rat model. METHODS: hUMSCs and hAD-MSCs were isolated from umbilical cord stroma and adipose tissue, respectively. The expression of Mesenchymal (CD73, CD90 and CD105) and hematopoietic (CD45 and CD133) markers of hUMSCs and hAD-MSCs were confirmed by flow cytometry. Alzheimer's rat model was created by ß-amyloid 1-42 injection into the hippocampus and confirmed by Morris Water Maze and immunohistochemical staining. hUMSCs and hAD-MSCs were injected in Alzheimer's rat model, intravenously. Deposition of ß-amyloid in the CA1 of hippocampus was assayed 3 months after cell administration. The expression of synaptophysin and GAP43 proteins was assessed by Western blot. Neural death was assessed by Nissl staining. RESULTS: The data obtained from flow cytometry showed that surface mesenchymal and hematopoteic markers of the fibroblastic like cells isolated from adipose tissue and umbilical cord were expressed highly in hUMSCs and mostly in hAD-SCs. Transplantation of MSCs reduced ß-amyloid deposition in the hippocampus of the AD rats compared to the ß-amyloid group. The rate of neuronal cell death in the hippocampus of the ß-amyloid-treated rats was significantly increased compared to that of the control group. The percentage of apoptotic cells in this group was 72.98 ± 1.25, which was significantly increased compared to the control group. Transplantation of either hUMSCs or hAD-SCs, respectively, resulted in a significant reduction in the apoptotic rate of the neuronal cells in the hippocampus by 39.47 ± 0.01 (p = 0.0001) and 43.23 ± 0.577 (p = 0.001) compared to the ß-amyloid group. MSC transplantation resulted in a significant up-regulation in the expression levels of both synaptogenic (synaptophysin) and neurogenic markers (GAP43) by 1.289 ± 0.112 (P = 0.02) and 1.112 ± 0.106 (P = 0.005) fold in the hUMSCs-treated group and 1.174 ± 0.105 (P = 0.04) and 0.978 ± 0.167 (P = 0.008) fold in the hAD-SCs-treated group, respectively. CONCLUSION: Intravenous injection of hUMSCs and hAD-MSCs is a safe approach that improves synaptic function and neurogenesis via up-regulation of synaptophysin and GAP43 protein expression levels, respectively, in Alzheimer's model. Intravenous injection of both applied SCs could improve learning and cognitive impairment induced by ß A42 injection.

Human adipose-derived stem cells reduce receptor-interacting protein 1, receptor-interacting protein 3, and mixed lineage kinase domain-like pseudokinase as necroptotic markers in rat model of Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) is a constant, developing brain impairment that is described as the aggregation of misfolded amyloid-beta-peptide (Ab) and abnormal tau protein in the brain. Stem cell therapy became a favorable candidate for the regeneration of neurodegenerative disorders like AD, but there is still shortage of knowledge about the underlying mechanisms. The goal of this survey was the determination of the necroptotic pathway as the possible mechanism for the effect of human adipose-derived stem cells (hADSCs) in the rat model of AD. MATERIALS AND METHODS: Twelve rats were consumed, dividing into four groups: Control, sham, AD model and AD + stem cell groups. We utilized Nissl and Thioflavin S staining for determining histological changes and immunofluorescent techniques for evaluating necroptotic markers in different regions of the hippocampus. RESULTS: The confirmation of AD model was approved with histological examination. The findings indicated more distinct Thio-S stain and an increased number of dead cells in AD rats comparing to other groups. Alternatively, the dead cells number in the CA3 area significantly lessened in AD + stem cell group comparing to AD group. Data showed that hADSCs significantly decreased the expression of necroptotic markers (receptor-interacting protein 1, receptor-interacting protein 3 and mixed lineage kinase domain-like pseudokinase (MLKL)) in AD + stem cell group compared to AD group in different regions of the hippocampus. CONCLUSION: Our findings revealed that the intravenous injection of hADSCs reduced necroptosis and consequently declined the death of neuronal cells in the hippocampus of AD rats.

Olfactory mucosa stem cells: An available candidate for the treatment of the Parkinson's disease.

Olfactory ectomesenchymal stem cells (OE-MSCs) possess the immunosuppressive activity and regeneration capacity and hold a lot of promises for neurodegenerative disorders treatment. This study aimed to determine OE-MSCs which are able to augment and differentiate into functional neurons and regenerate the CNS and also examine whether the implantation of OE-MSCs in the pars compacta of the substantia nigra (SNpc) can improve Parkinson's symptoms in a rat model-induced with 6-hydroxydopamine. We isolated OE-MSCs from lamina propria in olfactory mucosa and characterized them using flow cytometry and immunocytochemistry. The therapeutic potential of OE-MSCs was evaluated by the transplantation of isolated cells using a rat model of acute SN injury as a Parkinson's disease. Significant behavioral improvement in Parkinsonian rats was elicited by the OE-MSCs. The results demonstrate that the expression of PAX2, PAX5, PITX3, dopamine transporter, and tyrosine hydroxylase was increased by OE-MSCs compared to the control group which is analyzed with real-time polymerase chain reaction technique and immunohistochemical staining. In the outcome, the transplantation of 1,1'-dioctadecyl-3,3,3'3'-tetramethyl indocarbocyanine perchlorate labeled OE-MSCs that were fully differentiated to dopaminergic neurons contribute to a substantial improvement in patients with Parkinson's. Together, our results provide that using OE-MSCs in neurodegenerative disorders might lead to better neural regeneration.