Alzheimer's disease is the most common neurodegenerative disease, globally affecting almost a third of people over 85 years of age. Currently available treatments only improve the quality of life, but do not affect the course of the disease itself. Mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) can restore damaged nerve tissue and slow disease progression due to their broad differentiation capabilities and low chance of immune rejection, therefore they represent a great potential for Alzheimer's disease therapy. By mimicking certain aspects of neuropathology and behavioral features, mouse models of Alzheimer's disease are useful for testing the impact of transplanted stem cells (SCs) on the pathophysiological features of the disease and help reduce the gap between preclinical and clinical trials.
The purpose of the master's thesis is to determine whether and how transplanted SCs affect the cognitive properties of mouse models of Alzheimer's disease and to investigate their effects on cells and mechanisms that are altered in the disease.
We performed a systematic review of research in the online bibliographic databases Pubmed and Science Direct. We defined a search profile based on which we obtained preclinical studies on the effects of MSC and iPSC in mouse models of Alzheimer's disease. The selection was carried out in the accordance with the PRISMA guidelines. We limited the search profile for the field of application of MSC to research conducted after 2018, while we did not apply the research time limit in the field of iPSC.
The 16 studies that met our inclusion criteria were analyzed by year of publication, country in which they were conducted, species and gender of mouse model, and site of MC administration. We then presented the main characteristics of each study including the age of the mouse model, the type of MC used, the amount of MC injected, and the cognitive tests performed. In five studies demonstrated improvement of memory and spatial memory after MSC transplantation. Improvement of spatial memory was also shown in one study after iPSC transplantation and in two studies after induced pluripotent stem cell-derived neural precursors (iPSC-NPC) transplantation.
The results reported the influence of MSCs and iPSCs on improving spatial memory and deposition of amyloid plaques in mouse models of Alzheimer's disease. In addition, preclinical research has demonstrated the effect of MSCs on lowering the concentration of phosphorylated protein tau, increasing synaptic density, mitigating the decline of nerve tissue, and influencing microglia overactivity and oxidative stress. Although the mechanism of action by which MCs improve cognitive properties in mouse models of the disease is not yet fully elucidated, the discussed preclinical studies have shown that MCs have a good potential for the treatment of Alzheimer's disease.
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