Neural stem cell secretome and its role in the treatment of neurodegenerative disorders

Abstract

Neurological diseases in the central nervous system are mostly characterized by the failure of endogenous repair to restore tissue damage and salvage lost function. Currently, studies have shown that neural stem cell transplantation provides a good therapeutic effect on neurological diseases. For this reason, neural stem cell transplantation has been explored as a cell replacement therapy. Although transplanted cells can replace cells lost during or post central nervous system injury, many studies have shown that this mechanism is insufficient as most of these newly formed cells fail to integrate and eventually die. Although it was initially thought that neural stem cell could only replace lost cells, recent experiments have shown that transplanted neural stem cell can also play bystander roles such as neuroprotection and immune regulation, promote tissue repair by preventing tissue damage, interfere with pathogenic processes, or by rescuing endogenous nerve cells. However, compelling evidence has raised concerns about this bystander effect, which can be caused by several biologically active molecules (collectively known as the secretome) produced by neural stem cells. These results also raise the possibility of the neural stem cell secretome as a potential candidate for neural stem cell transplantation therapies based on the bystander effect. A better understanding of the molecules and mechanisms of this effect is of critical importance for neural stem cell-based therapies. This review aims to discuss the function and application of neural stem cell secretome in the treatment of neurodegenerative disorders.

Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study

“…The paradigm that NPC transplantation acts only by structural cell replacement has been reconsidered. Indeed, NPCs can shape their behavior and fate according to the central nervous system (CNS) microenvironment, maintaining an undifferentiated phenotype 3 . NPCs exert trophic support, immunomodulation and metabolic signaling via paracrine mechanisms and cell-to-cell interaction, the so-called bystander effect, which promotes neuroprotection and tissue repair by re-establishing the functional interactions between neural and glial cells or rousing endogenous neural cells 4 – 8 .…”

Stem Cell-based Therapeutic and Diagnostic Approaches in Alzheimer's Disease

“…Altogether, the clinical application of stem cells stays a daunting task since most grafted stem cells fail to integrate appropriately with resident circuits with an elusive mechanism [ 159 ]. To solve this issue, researchers have developed multiple laboratory methods to empower stem cells’ performance and modulate neural niches.…”

Oxidative-Signaling in Neural Stem Cell-Mediated Plasticity: Implications for Neurodegenerative Diseases

“…Notably, several studies showed that stem cells trigger tissue repair due to their ability to secrete molecules with a beneficial impact on the damaged tissue, rather than to their capacity to differentiate into the required differentiated cells [87]. These secreted factors are referred to as cell secretome and include growth factors, cytokines, chemokines and exosomes [4,88] found in the cell culture medium (conditioned medium). The soluble factors and vesicles secreted by stem cells may therefore act directly by mediating intra-cellular pathways in injured cells, or indirectly, by inducing the secretion of functionally active products from adjacent tissues [87].…”