Mesenchymal Stem Cells as Treatment for Behavioral Deficits and Neuropathology in the 5xFAD Mouse Model of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is characterized by a progressive loss of memory and other cognitive disturbances. The neuropathology of AD includes the major hallmarks of toxic amyloid-β oligomer accumulation and neurofibrillary tangles, as well as increased oxidative stress, cholinergic dysfunction, synapse loss, changes in endogenous neurotrophic factors, and overall degeneration of the brain. Adult mesenchymal stem cells (MSCs) offer the potential for a readily available treatment that would be long lasting, have low likelihood of rejection, and could target a variety of pathological deficits. MSCs have been shown to be effective in alleviating symptoms in some transgenic models of AD, but the optimal location for transplanting MSCs has yet to be determined. In the present study, the behavioral effects of transplantation of MSCs into the lateral ventricles, the hippocampus, or both of these regions were compared in the 5xFAD mouse model of AD. The results indicate that MSC transplants effectively reduce learning deficits in the 5xFAD mouse model and demonstrate a clear impact of MSCs on the levels of Aβ42 in the brains of 5xFAD mice. Overall, these findings support the hypothesis that MSCs may be a viable treatment for AD, especially when injected into the lateral ventricles.

Effects of Bone-Marrow–Derived MSC Transplantation on Functional Recovery in a Rat Model of Spinal Cord Injury

“…Though argued to contribute to cell death by affecting the DNA, previous studies by our group have observed no aberrant cell growth in response to Hoechst nuclear staining. 16 – 18 , 22 This stain was also determined to be adequately specific to the transplanted cells, as no efflux of the Hoechst dye to endogenous structures was observed in any of the transplanted tissue samples. Likewise, as MSCs are nonimmunogenic, no abnormal growths beyond the expected trauma-induced histopathology were observed.…”

“…Mesenchymal stem cells (MSCs) are obtained from tissues of mesodermal origins, can be found in fat, blood, and bone marrow, and have shown promising results in the treatment of many degenerative and traumatic conditions, including Huntington's disease, 16 Alzheimer's disease, 17 stroke, 18 and SCI. 19 These cells show properties such as low immunogenicity, secretion of trophic support factors, and the ability to differentiate into multiple lineages.…”

Cell motility and migration as determinants of stem cell efficacy

“…As an example, the use of SC for the transport of oncolytic agents in cancer therapies requires their active migration to the tumour site [6] . Poor to non-existent in vivo migration of surgically transplanted neural stem cells (NSC) [7] or MSC [8] reduced the grafted cells ability to reach multiple disease-affected areas of the brain. The requirement not only to migrate, but to do it as fast as possible is of special importance for oncovirolytic cancer therapy.…”

Exploring the Potential of Mesenchymal Stem Cell-Based Therapy in Mouse Models of Vascular Cognitive Impairment

“…Other than differences in vascular compromise, the cell concentration could have also factored in affecting the overall survival of the VCI-subjected mice. A former group injected 2 × 10 5 MSCs suspended in 2 µL of Hank's balanced salt solution (HBSS) bilaterally into the lateral ventricles of 6-month-old 5xFAD mice [40]. The authors proposed that therapeutic benefits were enhanced when MSCs were bilaterally injected into the lateral ventricles and not the bilateral hippocampi.…”