Abstract

Pathologies of the central nervous system are characterized by loss of brain tissue and neuronal function which cannot be adequately restored by endogenous repair processes. This stresses the need for novel treatment options such as cell-based therapies that are able to restore damaged tissue or stimulate repair. This study investigated the neuroregenerative potential of the conditioned medium of human dental pulp stem cells (CM-hDPSCs) on neural stem cell (NSC) proliferation and migration as well as on neurite outgrowth of primary cortical neurons (pCNs). Additionally, the effect of leukocyte- and platelet-rich fibrin (L-PRF) priming on the neuroregenerative potential of the hDPSC secretome on NSCs and pCNs was evaluated. L-PRF contains factors that enhance stem cell-induced regeneration, but its effect on hDPSC-mediated neuroregeneration is unknown. This study demonstrated that CM-hDPSCs enhanced neuritogenesis. Moreover, CM-hDPSCs had a chemoattractant effect on NSCs. Although priming hDPSCs with L-PRF increased brain-derived neurotrophic factor secretion, no additional effects on the paracrine-mediated repair mechanisms were observed. These data support the neuroregenerative potential of hDPSCs, and although priming had no additional effect, the potential of L-PRF-primed hDPSCs on distinct regenerative mechanisms remains to be clarified.

Highlights

  • Pathologies of the central nervous system (CNS), such as stroke, are one of the main causes of death and new cases of permanent disabilities which are characterized by tissue damage and loss of brain function [1]

  • The lost tissue can only be partially reconstituted by the host, for example, via endogenous neural stem cells (NSCs) that migrate towards the injury

  • Semiquantitative analysis of the relative pixel density of these proteins of interest suggested that none of these mediators were more abundant in either leukocyte- and platelet-rich fibrin (L-PRF) fractions (Figure 2(c)) as depicted by green squares in Figures 2(a) and 2(b)

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Summary

Introduction

Pathologies of the central nervous system (CNS), such as stroke, are one of the main causes of death and new cases of permanent disabilities which are characterized by tissue damage and loss of brain function [1]. The lost tissue can only be partially reconstituted by the host, for example, via endogenous neural stem cells (NSCs) that migrate towards the injury This regenerative response is ineffective and novel therapies, such as cell-based therapies are needed for treating these disorders. It is described that hDPSCs can enhance neuroregeneration via several mechanisms, including cell replacement, neuroprotection, and immunomodulation, and by promoting neuroplasticity and angiogenesis [7, 9,10,11,12,13] As these mechanisms were mainly thought to be mediated by paracrine actions of the hDPSCs, our group recently investigated the effect of the hDPSC secretome on human

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