Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells

Cellular heterogeneity presents an important challenge to the development of cell-based therapies where there is a fundamental requirement for predictable and reproducible outcomes. Transplanted Dental Pulp Stem/Progenitor Cells (DPSCs) have demonstrated early promise in experimental models of spina...

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Main Authors: Fraser I. Young, Vsevolod Telezhkin, Sarah J. Youde, Martin S. Langley, Maria Stack, Paul J. Kemp, Rachel J. Waddington, Alastair J. Sloan, Bing Song
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/1290561
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author Fraser I. Young
Vsevolod Telezhkin
Sarah J. Youde
Martin S. Langley
Maria Stack
Paul J. Kemp
Rachel J. Waddington
Alastair J. Sloan
Bing Song
author_facet Fraser I. Young
Vsevolod Telezhkin
Sarah J. Youde
Martin S. Langley
Maria Stack
Paul J. Kemp
Rachel J. Waddington
Alastair J. Sloan
Bing Song
author_sort Fraser I. Young
collection DOAJ
description Cellular heterogeneity presents an important challenge to the development of cell-based therapies where there is a fundamental requirement for predictable and reproducible outcomes. Transplanted Dental Pulp Stem/Progenitor Cells (DPSCs) have demonstrated early promise in experimental models of spinal cord injury and stroke, despite limited evidence of neuronal and glial-like differentiation after transplantation. Here, we report, for the first time, on the ability of single cell-derived clonal cultures of murine DPSCs to differentiate in vitro into immature neuronal-like and oligodendrocyte-like cells. Importantly, only DPSC clones with high nestin mRNA expression levels were found to successfully differentiate into Map2 and NF-positive neuronal-like cells. Neuronally differentiated DPSCs possessed a membrane capacitance comparable with primary cultured striatal neurons and small inward voltage-activated K+ but not outward Na+ currents were recorded suggesting a functionally immature phenotype. Similarly, only high nestin-expressing clones demonstrated the ability to adopt Olig1, Olig2, and MBP-positive immature oligodendrocyte-like phenotype. Together, these results demonstrate that appropriate markers may be used to provide an early indication of the suitability of a cell population for purposes where differentiation into a specific lineage may be beneficial and highlight that further understanding of heterogeneity within mixed cellular populations is required.
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spelling doaj-art-6509d82a57d045c7a208ed29b28e05252025-02-03T06:01:39ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/12905611290561Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor CellsFraser I. Young0Vsevolod Telezhkin1Sarah J. Youde2Martin S. Langley3Maria Stack4Paul J. Kemp5Rachel J. Waddington6Alastair J. Sloan7Bing Song8Oral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UKCardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UKOral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UKOral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UKOral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UKCardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UKOral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UKOral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UKOral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UKCellular heterogeneity presents an important challenge to the development of cell-based therapies where there is a fundamental requirement for predictable and reproducible outcomes. Transplanted Dental Pulp Stem/Progenitor Cells (DPSCs) have demonstrated early promise in experimental models of spinal cord injury and stroke, despite limited evidence of neuronal and glial-like differentiation after transplantation. Here, we report, for the first time, on the ability of single cell-derived clonal cultures of murine DPSCs to differentiate in vitro into immature neuronal-like and oligodendrocyte-like cells. Importantly, only DPSC clones with high nestin mRNA expression levels were found to successfully differentiate into Map2 and NF-positive neuronal-like cells. Neuronally differentiated DPSCs possessed a membrane capacitance comparable with primary cultured striatal neurons and small inward voltage-activated K+ but not outward Na+ currents were recorded suggesting a functionally immature phenotype. Similarly, only high nestin-expressing clones demonstrated the ability to adopt Olig1, Olig2, and MBP-positive immature oligodendrocyte-like phenotype. Together, these results demonstrate that appropriate markers may be used to provide an early indication of the suitability of a cell population for purposes where differentiation into a specific lineage may be beneficial and highlight that further understanding of heterogeneity within mixed cellular populations is required.http://dx.doi.org/10.1155/2016/1290561
spellingShingle Fraser I. Young
Vsevolod Telezhkin
Sarah J. Youde
Martin S. Langley
Maria Stack
Paul J. Kemp
Rachel J. Waddington
Alastair J. Sloan
Bing Song
Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells
Stem Cells International
title Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells
title_full Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells
title_fullStr Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells
title_full_unstemmed Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells
title_short Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells
title_sort clonal heterogeneity in the neuronal and glial differentiation of dental pulp stem progenitor cells
url http://dx.doi.org/10.1155/2016/1290561
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