Potential Effects of MSC-Derived Exosomes in Neuroplasticity in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most common type of dementia affecting regions of the central nervous system that exhibit synaptic plasticity and are involved in higher brain functions such as learning and memory. AD is characterized by progressive cognitive dysfunction, memory loss and behavioral disturbances of synaptic plasticity and energy metabolism. Cell therapy has emerged as an alternative treatment of AD. The use of adult stem cells, such as neural stem cells and Mesenchymal Stem Cells (MSCs) from bone marrow and adipose tissue, have the potential to decrease cognitive deficits, possibly by reducing neuronal loss through blocking apoptosis, increasing neurogenesis, synaptogenesis and angiogenesis. These processes are mediated primarily by the secretion of many growth factors, anti-inflammatory proteins, membrane receptors, microRNAs (miRNA) and exosomes. Exosomes encapsulate and transfer several functional molecules like proteins, lipids and regulatory RNA which can modify cell metabolism. In the proteomic characterization of the content of MSC-derived exosomes, more than 730 proteins have been identified, some of which are specific cell type markers and others are involved in the regulation of binding and fusion of exosomes with adjacent cells. Furthermore, some factors were found that promote the recruitment, proliferation and differentiation of other cells like neural stem cells. Moreover, within exosomal cargo, a wide range of miRNAs were found, which can control functions related to neural remodeling as well as angiogenic and neurogenic processes. Taking this into consideration, the use of exosomes could be part of a strategy to promote neuroplasticity, improve cognitive impairment and neural replacement in AD. In this review, we describe how exosomes are involved in AD pathology and discuss the therapeutic potential of MSC-derived exosomes mediated by miRNA and protein cargo.

Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

“…The tangles also contain small pieces of microtubules, and indeed, due to the loss of function of the tau protein, the microtubule dynamics and function are impaired in both anterograde and retrograde trafficking along the axons of molecules/complexes/organelles. As a consequence, in a process lasting many years, cortical neurons and synapses are lost in brain areas involved in memory and learning, especially the prefrontal cortex and hippocampus [256,257]. Eventually β-amyloid plaques and neurofibrillary tangles may also extend to other brain formations [258] such as limbic and association areas [259].…”

“…Eventually β-amyloid plaques and neurofibrillary tangles may also extend to other brain formations [258] such as limbic and association areas [259]. As the disease progresses, aggregates of Aβ are also found in motor areas, CSF, and even in regions not directly belonging to brain, such as the eyes [257].…”

Efficient One-Step Induction of Human Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) Produces MSC-Derived Neurospheres (MSC-NS) with Unique Transcriptional Profile and Enhanced Neurogenic and Angiogenic Secretomes

“…But it remains unclear why the reported studies demonstrated much less efficacy because we could consistently repeat our results in multiple settings, even when using MSCs passaged up to 30. Paracrine effects play an important role in mesenchymal stem cell transplantation clinical trials [28][29][30]. Some studies have shown MSCs, especially UC-MSC, to express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis [31][32][33].…”

Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review

“…Neurodegenerative conditions are of special interest due to their affect on cognitive functions. Alzheimer's disease (AD) is an elaborated neurodegenerative condition, caused by β-amyloid peptide (Aβ) accumulation outside neurons and neurofibrillary tangles (NFT) consisting of hyperphosphorylated tau protein in cells [69]. Another neurodegenerative disorder is amyotrophic lateral sclerosis (ALS) resulting in general in impairment of human motor system and death predominantly because of respiratory failure.…”