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

Maxim Karagyaur,Vsevolod Tkachuk,Stalik Dzhauari,Pavel Malkov,Vladimir Popov,Anastasia Efimenko,Natalia Aleksandrushkina,Natalia Danilova,Nataliya Basalova,Mariya Skryabina,Georgy Sagaradze

doi:10.3390/pharmaceutics13122031

Maxim Karagyaur, Vsevolod Tkachuk + Show 9 more

Open Access

https://doi.org/10.3390/pharmaceutics13122031

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Journal: Pharmaceutics	Publication Date: Nov 29, 2021
Citations: 12	License type: CC BY 4.0

Affiliation: Lomonosov Moscow State University

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.

Highlights

Multipotent mesenchymal stromal cells (MSCs) were initially identified by Friedenstein et al and defined as plastic-adherent fibroblast colony-forming units with clonogenic capacity [1]
The results of the pilot study showed that hMSC1x secretome has potential therapeutic activity, but it turns out to be less effective than the positive control brain-derived neurotrophic factor (BDNF) secretome (Figure 1b)
HMSC1x secretome did not have a significant effect on survival (Figure 1a) and the alleviation of neurological deficits in experimental animals, it contributed to the preservation of long-term memory in rats

Summary

Introduction

Multipotent mesenchymal stromal cells (MSCs) were initially identified by Friedenstein et al and defined as plastic-adherent fibroblast colony-forming units with clonogenic capacity [1]. MSCs were found in the perivascular niche and interstitial compartment of a wide variety of tissues [2]. Multiple studies have demonstrated the direct antiapoptotic activity of MSCs as well as their ability to stimulate angiogenesis and neurogenesis, and to suppress the immune response [5,6,7,8,9]. This variety of pro-regenerative activities makes MSCs a perspective tool for clinical therapy [10]

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