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

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

Intranasal Administration of Undifferentiated Oligodendrocyte Lineage Cells as a Potential Approach to Deliver Oligodendrocyte Precursor Cells into Brain

Oligodendrocyte precursor cell (OPC) migration is a mechanism involved in remyelination; these cells migrate from niches in the adult CNS. However, age and disease reduce the pool of OPCs; as a result, the remyelination capacity of the CNS decreases over time. Several experimental studies have introduced OPCs to the brain via direct injection or intrathecal administration. In this study, we used the nose-to brain pathway to deliver oligodendrocyte lineage cells (human oligodendroglioma (HOG) cells), which behave similarly to OPCs in vitro. To this end, we administered GFP-labelled HOG cells intranasally to experimental animals, which were subsequently euthanised at 30 or 60 days. Our results show that the intranasal route is a viable route to the CNS and that HOG cells administered intranasally migrate preferentially to niches of OPCs (clusters created during embryonic development and adult life). Our study provides evidence, albeit limited, that HOG cells either form clusters or adhere to clusters of OPCs in the brains of experimental animals

Exosomes and Biomaterials: In Search of a New Therapeutic Strategy for Multiple Sclerosis

Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited its application. A series of recent studies have focused on the cell secretome, showing it to provide the most benefits of cell therapy. Exosomes are a key component of the cell secretome, participating in the transfer of bioactive molecules. These nano-sized vesicles offer many therapeutical advantages, such as the capacity to cross the blood-brain barrier, an enrichable cargo, and a customizable membrane. Moreover, integrating of biomaterials into exosome therapy could lead to new tissue-specific therapeutic strategies. In this work, the use of exosomes and their integration with biomaterials is presented as a novel strategy in the treatment of MS