Potential of bone marrow mesenchymal stem cells in management of Alzheimer's disease in female rats

AbstractAlzheimer's disease (AD) has been called the disease of the century with significant clinical and socioeconomic impacts.Pharmacological treatment has limited efficacy and only provides symptomatic relief without long-term cure. Accordingly,thereisanurgentneedtodevelopnovelandeffectivemedicationsforAD.Stemcell-basedtherapyisapromisingapproachtohandling neurodegenerative diseases. Therefore, the current study aimed to explore the possible therapeutic role of singleintravenous injection of bone marrow derived mesenchymal stem cells (BM-MSCs) after 4 months in management of AD inthe experimental model. The work also extended to compare the therapeutic potential of BM-MSCs with 2 conventionaltherapies of AD; rivastigmine and cerebrolysin administered daily. BM-MSCs were able to home at the injured brains andproducedsignificantincreasesinthenumberofpositivecellsforcholineacetyltransferase(ChAT)andsurvivinexpression,aswell as selective AD indicator-1 (seladin-1) and nestin gene expression. Histopathological examination indicated that BM-MSCscouldremovebeta-amyloidplaquesfromhippocampus.Significantimprovementinthesebiomarkerswassimilartoorbetter sometimes than the reference drugs, clearly showing the potential therapeutic role of BM-MSCs against AD throughtheir anti-apoptotic, neurogenic and immunomodulatory properties.Keywords: Alzheimer’s disease; Bone marrow mesenchymal stem cells; Cerebrolysin; Rats; RivastigmineIntroductionOver 30 million people suffer from dementia worldwide,with numbers firstly dramatically increasing and secondly,with no cure in sight (Ballard et al., 2011). Of all dementingdisorders, Alzheimer’s disease (AD) is the most prevalent.Alzheimer’s disease is progressive disorder in which braincells deteriorate, resulting in the loss of cognitive functions,primary memory, judgment, reasoning, movement coordi-nation,andpatternrecognition(Karlawishetal.,2005).Themost significant pathological findings in the brains affectedby AD are senile plaques, neurofibrillary tangles, anddegeneration of neuronal population in special regionsparticularlyintheareasconnectedtothecerebralcortexandhippocampus (Gotz and Ittner, 2008). The most notableneurons in these regions are the cholinergic neurons,GABAergic neurons, dopaminergic neurons, norepineph-rinergicneurons, and serotonergic neurons—mostof whichare all seriously degenerated (Dickson et al., 2005).Cholinesterase inhibition represents an important thera-peutic strategy in the management of AD. Cholinesteraseinhibitors increase the availability of acetylcholine throughinhibition of its destruction. Therefore, they could enhancecholinergic transmission in the brain and improve thesymptoms of AD (Blennow et al., 2006). Rivastigmine is oneof the cholinesterase inhibitors that affect both acetylcholin-esterase and butyrylcholinesterase (Jann, 2000). While inanother strategy depends on neurotrophic and neuroprotec-tiveeffects,cerebrolysinwhichisapeptidergicdrugobtainedbystandardizedenzymaticbreakdownfrompurifiedporcinebrain preparations (Riley et al., 2006), is effective in ADtreatmentinearliertrials(Alvarezetal.,2006).ThecurrentlyapprovedtreatmentsforADdonothalttheprogressionofthedisease, and have provided marginal therapeutic benefits.Therefore, there is an urgent need to develop novel andeffective medications for AD (Tayeb et al., 2012).In recent years, mesenchymal stem cells (MSCs) havebeen considered as a promising therapeutic strategy for