Mesenchymal Stem Cell-Derived Exosomes Versus its Conditioned Medium in Amelioration of Hippocampal Rat Model of Alzheimer's Disease, Behavioral, Biochemical, Histological and Immunohistochemical Study

Document Type : Original Article

Authors

1 Department of Histology and Cell Biology, Minia University, Minia

2 1Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia,

3 Department of Medical Pharmacology, Faculty of Medicine, Minia University, Minia

4 Department of Biochemistry, Faculty of Veterinary, Cairo University, Cairo,

5 Department of Animal and Poultry Management and Wealth Development, Faculty of Veterinary, Beni-Suef University, Beni-Suef, Egypt

6 Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia,

Abstract

Introduction: Alzheimer's disease is the most common form of dementia. Recently, mesenchymal stem cells-conditioned
medium and exosomes have lately been employed in several therapeutic investigations.
Aim of work: To demonstrate hippocampus’s biochemical, histological and immunohistochemical changes in albino rats after
induction of Alzheimer and to evaluate the role of mesenchymal stem cells-conditioned medium versus exosomes on the albino
rat Alzheimer model.
Materials and Methods: Thirty-two rats were used in this study plus ten rats were used in the preparation of mesenchymal stem
cells derived conditioned media and exosomes. Rats were divided into four groups; Control, Alzheimer group, Conditioned
media and Exosome treated group. Behavioral tests were performed. The hippocampi were prepared for biochemical,
histological and immunohistochemical study.
Results: The Alzheimer group showed various behavioral changes. Rats also showed significant changes in hippocampal
malondialdehyde, tumor necrotic factor, total antioxidant capacity, acetylcholine esterase and monoamine oxidase.
Microscopically, hippocampi showed degenerated neurons as well as argyrophilic neurofibrillary tangles and amyloid
plaque formation. The conditioned medium and exosomes treated groups displayed biochemical, functional and structural
improvement with reduced argyrophilic neurofibrillary tangles and amyloid plaque formation. Treatment with exosomes
was superior to conditioned medium as they improved neuronal function, regulated astrocyte and microglial activities and
enhanced regenerative changes.
Conclusions: The conditioned medium and exosomes minimized Alzheimer - hippocampal associated biochemical, histological
and immunohistochemical degenerative changes with better effect with exosome treatment. These results may pave the future
for using exosomes as an effective adjuvant therapy in Alzheimer patients.

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