MSC Secretome as a Promising Tool for Neuroprotection and Neuroregeneration in a Model of Intracerebral Hemorrhage

Abstract

Multipotent mesenchymal stromal cells (MSCs) are considered to be critical contributors to injured tissue repair and regeneration, and MSC-based therapeutic approaches have been applied to many peripheral and central neurologic disorders. It has been demonstrated that the beneficial effects of MSC are mainly mediated by the components of their secretome. In the current study, we have explored the neuroprotective potential of the MSC secretome in a rat model of intracerebral hemorrhage and shown that a 10-fold concentrated secretome of human MSC and its combination with the brain-derived neurotrophic factor (BDNF) provided a better survival and neurological outcome of rats within 14 days of intracerebral hemorrhage compared to the negative (non-treated) and positive (BDNF) control groups. We found that it was due to the ability of MSC secretome to stimulate neuron survival under conditions of glutamate-induced neurotoxicity. However, the lesion volume did not shrink in these rats, and this also correlated with prominent microglia activation. We hypothesize that this could be caused by the species-specificity of the used MSC secretome and provide evidence to confirm this. Thus, we have found that allogenic rat MSC secretome was more effective than xenogenic human MSC secretome in the rat intracerebral hemorrhage model: it reduced the volume of the lesion and promoted excellent survival and neurological outcome of the treated rats.

Exosomal miR-132-3p from mesenchymal stromal cells improves synaptic dysfunction and cognitive decline in vascular dementia

“…Beside exosomes, there is evidence demonstrated that MSC secretome exerted an important role in regulating target cell functions, such as senescence [37], proliferation [20], and migration [38]. Recent studies also confirmed the protective effects of MSC secretome in neural function [39,40]. In this study, we showed that miR-132-3p could improve the effects of MSC EX in protecting neuron function.…”

Mesenchymal Stem Cell Application and Its Therapeutic Mechanisms in Intracerebral Hemorrhage

“…Many secreted trophic molecules as components of their secretome from MSCs transplanted by orthotopic and caudal vein injection facilitated the endogenous reparatory mechanism, which ultimately improved the recovery of neurological function after stroke ( Smith and Gavins, 2012 ; Shichinohe et al, 2015 ; Karagyaur et al, 2021 ). MSC transplantation is promising for promoting angiogenesis.…”

Urokinase-Type Plasminogen Activator Enhances the Neuroprotective Activity of Brain-Derived Neurotrophic Factor in a Model of Intracerebral Hemorrhage

“…Previously, this mechanism of brain tissue recovery (restricted microglial activation) had been assumed [ 20 ] but had not been confirmed experimentally. In contrast, hyperactivation of microglia increases inflammation, expands injury area and aggravates the outcome [ 21 ].…”