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 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.
Oral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UK; Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK.
Fraser I
FI
Young
Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UK; Department of Neuroscience, Physiology & Pharmacology, University College London, London WC1E 6BT, UK.
Vsevolod
V
Telezhkin
Oral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Sarah J
SJ
Youde
Oral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Martin S
MS
Langley
Oral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Maria
M
Stack
Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, UK.
Paul J
PJ
Kemp
Oral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Rachel J
RJ
Waddington
Oral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Alastair J
AJ
Sloan
Oral and Biomedical Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Bing
B
Song