Comparative Study between Bone Marrow Mesenchymal Stem Cells and Their Derived Exosomes on Neurological Dysfunction in Experimentally Induced Alzheimer Disease in Rat Model
Authors: Hamed Gehane M , Morsy Wessam Ezzat , Elnahrawy Esraa Ahmed Baioumy , ElHamid Manal Said Abd 
Published: November 2024

Abstract

Background
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that accounts for 50–70% of the cases of dementia. by 2025, the worldwide prevalence of AD will increase to 100 million or more. Various therapeutic approaches targeting amyloid Ab peptides have been explored, however, most of them did not exhibit positive outcomes in their phase III TRIALS.
AIM: The study was planned to compare the effect of bone marrow mesenchymal stem cells with their derived exosomes on neurological and cognitive dysfunction in experimentally induced alzheimer disease in RAT model.

Methods
The present study was performed on 40 adult albino male rats, weighing 160-220 grams. Rats included in the present study were randomly allocated into the following groups: Group I: Control RAT group (C; N = 10): RATS In this Group were injected intraperitoneally by saline 0.9% for 5 days two hours before the behavioral tests and then at day 5 by phosphate-buffered saline (PBS). group ii: experimentally induced alzheimer group (ALZ.; n = 10): rats in this group were injected intraperitoneally by lps for five consecutive days two hours before the behavioral tests and then at day 5 by phosphate-buffered saline (PBS). group iii: mesenchymal stem cell transplanted alzheimer group (ALZ./MSCS; n = 10): rats in this group were injected intraperitoneally by lps for five consecutive days two hours before the behavioral tests and then at day 5 they were transplanted intravenously (IV) with bone marrow mesenchymal stem cells. group IV: mesenchymal stem cells derived exosomes transplanted alzheimer group (ALZ./exosomes; n = 10): rats in this group were injected intraperitoneally by lps for five consecutive days two hours before the behavioral tests and then at day 5 they were transplanted intravenously (IV) with exosomes over 5 minutes and scarified after one month. body weight measurement and behavioral assessment were done at the start of the study and at the end of the study. on the day of sacrifice, brain tissue was collected for determination of amyloid-Β (aΒ) peptides, levels of acetylcholine (ach), inflammatory mediators as tumor necrosis factor Α (TNFΑ) and apoptotic markers as bax and bcl2 and blood sample were collected for assessment of serum malondialdehyde (MDA) and serum superoxide dismutase (SOD). histopathological examination of brain tissue sections was performed.

Results
During the 5 days of saline/Lipopolysaccharide injection, Mean escape latency time of Morris water maze test and pole climbing time of pole test were significantly shortened in control (C) group and significantly prolonged in Alz., Alz./MSCs and Alz./exosomes groups. One month after treatment: after phosphate buffer injection/stem cells transplantation/exosomes transplantation Mean escape latency time of Morris water maze test was significantly shortened in control (C), Alz./MSCs and Alz./exosomes groups; retention latency time of passive avoidance test was significantly prolonged in control (C), Alz./MSCs and Alz./exosomes groups and significantly decreased in Alz. Group; pole climbing time of pole test was significantly shortened in control (C), Alz./MSCs and Alz./exosomes groups; mean latency (riding) time of rotarod test was significantly prolonged in control (C) and Alz./exosomes groups. Alz./MSCs and Alz./exosomes groups showed significant decrease in Mean escape latency time of Morris water maze test and pole climbing time of pole test and showed significant increase retention latency time of passive avoidance test and mean latency (riding) time of rotarod test when compared to Alz. group. Also Alz./exosomes groups, showed significant decrease in Mean escape latency time of Morris water maze test and showed significant increase in retention latency time of passive avoidance test and mean latency (riding) time of rotarod test when compared to Alz./MSCs group. Biochemical markers: significant increase in levels of acetylcholine (Ach), Bcl2 and serum superoxide dismutase (SOD) and significant decrease of tumor necrosis factor α (TNFα), Amyloid-β (Aβ) peptides, BAX and serum malondialdehyde (MDA) levels in Mesenchymal stem cell transplanted Alzheimer group (Alz/MSCs) and Mesenchymal stem cells derived exosomes transplanted Alzheimer group (Alz./exosomes) in comparing to Alzheimer group (Alz).

Conclusion
These results highlighted the beneficial effects of MSCs-exosomes in AD treatment by tackling multiple key pathways of the disease pathogenesis.