Stimulation of the Migration and Expansion of Adult Mouse Neural Stem Cells by the FPR2-Specific Peptide WKYMVm.

Yang Woo Kwon,Jong Hyuk Yoon,Yeon Suk Jo,Youngsuk Seo,Sungwon Bae

doi:10.3390/life11111248

Yang Woo Kwon, Jong Hyuk Yoon + Show 3 more

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https://doi.org/10.3390/life11111248

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Abstract

Neural stem cells (NSCs) are multipotent cells capable of self-renewal and differentiation into different nervous system cells. Mouse NSCs (mNSCs) are useful tools for studying neurogenesis and the therapeutic applications of neurodegenerative diseases in mammals. Formyl peptide receptor 2 (FPR2), expressed in the central nervous system and brain, is involved in the migration and differentiation of murine embryonic-derived NSCs. In this study, we explored the effect of FPR2 activation in adult mNSCs using the synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met-NH2 (WKYMVm), an agonist of FPR2. After isolation of NSCs from the subventricular zone of the adult mouse brain, they were cultured in two culture systems—neurospheres or adherent monolayers—to demonstrate the expression of NSC markers and phenotypes. Under different conditions, mNSCs differentiated into neurons and glial cells such as astrocytes, microglia, and oligodendrocytes. Treatment with WKYMVm stimulated the chemotactic migration of mNSCs. Moreover, WKYMVm-treated mNSCs were found to promote proliferation; this result was confirmed by the expansion of mNSCs in Matrigel and the increase in the number of Ki67-positive cells. Incubation of mNSCs with WKYMVm in a supplement-free medium enhanced the survival rate of the mNSCs. Together, these results suggest that WKYMVm-induced activation of FPR2 stimulates cellular responses in adult NSCs.

Highlights

Neural stem cells (NSCs) can be applied to the recovery of neurological diseases, including central nervous system disorders and degenerative neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, stroke, and drug screening to develop therapeutic agents for these diseases [37,38]
The isolation and maintenance of NSCs from adults is important because differences in pathological characteristics, physiological functions, and molecular levels of NSCs can be directly analyzed according to neurological disease or disease progression [39,40]
In this study, adult Mouse NSCs (mNSCs) were isolated from the subventricular zone of the brain

Summary

Introduction

Neural stem cells possess stem cell properties such as self-renewal, long-term viability, and potential for differentiation into neural lineage cell types, including neurons and glial cell lineages such as astrocytes and oligodendrocytes [5,6,7] In addition to their ability to differentiate into multiple cell lineages, NSCs play an important role in the brain by secreting neurotrophic factors that regulate the local immune system, apoptosis, and homeostasis and protect the host cells [8,9,10]. Various studies have demonstrated that transplantation of NSCs improves the therapeutic efficacy in Alzheimer’s disease, Parkinson’s disease, and other neurological disease models [11,12] These studies suggest that NSCs enhance memory, cognition, behavior, and motor ability in neurodegenerative diseases by stimulating neuronal survival and synaptic function. NSCs can be a powerful tool for treating neurological diseases, the therapeutic efficacy of NSCs in clinical settings has not been satisfactory, so their application is insufficient

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