Abstract

Evidence from dental-related stem cells (DRSCs) suggests an enhanced potential for ectodermal lineage differentiation due to their neural crest origin. Growing evidence that DRSC cultures can produce cells with a neural crest-derived stem cell (NCSC)-like phenotype supports their potential for future therapeutic approaches for neurodegenerative diseases and nerve injuries. However, most of the evidence is limited to the characterization of DRSCs as NCSCs by detecting the expression of neural crest markers. Only a few studies have provided proof of concept of an improved neuro-glial differentiation or direct applicability in relevant models. In addition, a current problem is that several of the existing protocols do not meet manufacturing standards for transferability to a clinical scenario. This review describes the current protocols to obtain NCSCs from DRSCs and their characterization. Also, it provides important considerations from previous work where DRSCs were established and characterized as mesenchymal stromal cells but studied for their neuro-glial differentiation potential. The therapeutic advancement of DRSCs would depend on establishing protocols that can yield a neural crest-like phenotype efficiently, using appropriate manufacturing standards and testing them in relevant models of disease or injury. Achieving these conditions could then facilitate and validate the therapeutic potential of DRSC-NCSCs in regenerative therapies.

Highlights

  • The subgroup of adult stem cells defined in vitro as mesenchymal stromal cells (MSCs), are proposed as an ideal source of cells with therapeutic potential because of their multipotent differentiation, potential availability throughout life, and their possible use for autologous cell therapies

  • dental-related stem cells (DRSCs)-neural crest-derived stem cell (NCSC) for the generation of ectodermal lineages, as opposed to DRSCs characterized as MSCs

  • It would be necessary to extend the current knowledge of dental tissues as a potential source of human NCSCs to be used in regenerative medicine and in particular for neural-related issues

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Summary

Introduction

The subgroup of adult stem cells defined in vitro as mesenchymal stromal cells (MSCs), are proposed as an ideal source of cells with therapeutic potential because of their multipotent differentiation, potential availability throughout life, and their possible use for autologous cell therapies. It is believed that adult stem cells derived from the neural crest could be more efficient in deriving ectodermal lineages such as neurons and glia cells. The literature reviewed here introduces and describes how the neural crest developmental origin of DRSCs is used to obtain NCSCs. We will discuss the main strategies for obtaining a NCSC phenotype, their limitations, and the proposed advantages of using. DRSC-NCSCs for the generation of ectodermal lineages, as opposed to DRSCs characterized as MSCs. We have limited our discussion to work that clearly describes and characterizes. DRSCs as having a neural crest-like phenotype, excluding previous reports in which similar conditions may have been used, but where DRSCs were not defined molecularly as NCSCs

The Neural Crest and Its Adult Stem Cell Derivatives
Dental-Related Sources of Human Neural Crest-Derived Stem Cells
NCSCs Derived from Gingiva
Method
NCSCs Derived from Periodontal Ligament
NCSCs from Developing Teeth and the Adult Dental Pulp
NCSCs Derived from the Dental Pulp of Exfoliated Deciduous Teeth (SHEDs)
NCSCs Derived from the Apical Pulp or Apical Papilla (SCAPs)
NCSCs Derived from Dental Follicle
NCSCs Derived from the Dental Pulp
Considerations of Growth Conditions and Strategies for Isolation
EGF/FGF2 Containing Media
Small Molecules
Neurosphere Formation
Direct Isolation (Cell Sorting)
Important Considerations from Previous Reports of DRSCs Characterized as MSCs
Findings
Conclusions and Considerations for Future Applications
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