Mesenchymal stromal cells for the treatment of Alzheimer’s disease: Strategies and limitations

Abstract

Alzheimer’s disease (AD) is a major cause of age-related dementia and is characterized by progressive brain damage that gradually destroys memory and the ability to learn, which ultimately leads to the decline of a patient’s ability to perform daily activities. Although some of the pharmacological treatments of AD are available for symptomatic relief, they are not able to limit the progression of AD and have several side effects. Mesenchymal stem/stromal cells (MSCs) could be a potential therapeutic option for treating AD due to their immunomodulatory, anti-inflammatory, regenerative, antioxidant, anti-apoptotic, and neuroprotective effects. MSCs not only secret neuroprotective and anti-inflammatory factors to promote the survival of neurons, but they also transfer functional mitochondria and miRNAs to boost their bioenergetic profile as well as improve microglial clearance of accumulated protein aggregates. This review focuses on different clinical and preclinical studies using MSC as a therapy for treating AD, their outcomes, limitations and the strategies to potentiate their clinical translation.

Antioxidant and Antibacterial Properties of a Functional Sports Beverage Formulation

“…However, this adaptive mechanism has a limit, and so when ROS’ homeostatic role is surpassed, this deteriorates cellular damage and, subsequently, the aging process [ 69 ]. Moreover, MSCs’ use has been proposed for the treatment of several diseases such as cardiovascular and neurodegenerative, and, as a result, they have a central role in regenerative medicine [ 70 , 71 , 72 ]. However, oxidative stress leads to MSCs’ death, and thus impairs their therapeutic effects [ 73 ].…”

Mesenchymal Stem Cells Applications in Alzheimer's Disease

“…10 When treating AD with MSCs, MSCs proliferate astrocytes, metabolize glutamate and gamma-aminobutyrate, inhibit neural cell necrosis, and unleash growth factors (like brain-derived neurotrophic factor [BDNF]) to enhance neurogenesis by stimulating neural progenitor cells because of their antioxidant properties and antiapoptotic effects. 11,12 To stop additional tissue damage brought on by chronic neuroinflammation, MSCs also have modulatory effects on the immune system by bypassing or suppressing proinflammatory microglia (M1) activation and encouraging the activation of anti-inflammatory microglia (M2). Research has proven that MSCs can boost autophagy activation, which is likely to be the reason for the lysosomal clearance of Aβ plaques.…”

Novel Therapeutic Opportunities for Neurodegenerative Diseases with Mesenchymal Stem Cells: The Focus on Modulating the Blood-Brain Barrier

“…Irrespective of the neurodegenerative conditions discussed in this review, the limited efficacy observed in MSC treatment and the disparities between outcomes in mouse models and human clinical trials may be attributed to several factors. These include the specific source, culture, and isolation methods employed for MSCs, the dosage of transplanted cells, and the timing and route of delivery [ 195 , 196 , 197 , 198 , 199 , 200 ]. Furthermore, the accurate selection of patients and the identification of outcome measurements for assessing the success of MSC treatment are critical considerations that can significantly contribute to differences observed in clinical trials.…”

“…While endogenous repair mechanisms and injected MSCs can work in synergy during the repair of active plaques in relapsing-remitting MS, progressive forms of the disease witness a reduction in the function of reparative cells due to gliosis and the formation of fibrotic scars [ 236 ]. Similarly, in AD and PD, despite promising preclinical data, most clinical trials involving MSCs have yielded disappointing results due to the pathological variability corresponding to different stages of the diseases [ 196 , 198 ]. This heterogeneity in disease stages and phases introduces considerable variability across trials, both in terms of the therapeutic windows (spanning from acute to chronic stroke stages) and the routes of administration [ 215 , 216 , 217 , 237 , 238 , 239 ].…”