Differentiation of stem cells derived from carious teeth into dopaminergic-like cells.
OBJECTIVE
To investigate whether dental pulp stem cells from carious teeth (DPSCs-CT) can differentiate into functional dopaminergic-like (DAergic) cells and provide an alternative cell source in regenerative medicine.


METHODS
Dental pulp stem cells from healthy (DPSCs) and carious teeth (DPSCs-CT) were isolated from young donors. Both cell lines were expanded in identical culture conditions and subsequently differentiated towards DAergic-like cells using pre-defined dopaminergic cocktails. The dopaminergic efficiencies were evaluated both at gene and protein as well as at secretome levels.


RESULTS
The efficiency of DPSCs-CT to differentiate into DAergic-like cells was not equivalent to that of DPSCs. This was further reflected in both gene and protein generation whereby key neuronal markers such as nestin, NURR1 and beta-III-tubulin were expressed significantly lower as compared to differentiated DPSCs (P < 0.05). In addition, expressions of transcriptomes related to neurogenesis revealed downregulation of more than 50% of the genes as compared to differentiated DPSC (P < 0.05). Amongst the notable genes were those from the transcription factors family (FLNA, MEF2C, NEUROG2), signalling pathway family (DLL1, Notch1, TGF-β1), neuro-inducer family (BDNF) and cell communication family (APBB1).


CONCLUSIONS
DPSCs-CT were able to differentiate into DAergic-like cells but not as efficiently as DPSCs. As such, prior to use in regenerative medicine, stem cells from any source should be thoroughly investigated beyond conventional benchmarks such as that proposed by the International Society for Cellular Therapy (ISCT).
GMP-compliant stem cells laboratory, Hygieia Innovation, Persiaran Seri Perdana, Federal Territory of Putrajaya, Putrajaya, Malaysia.|Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
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Gnanasegaran
GMP-compliant stem cells laboratory, Hygieia Innovation, Persiaran Seri Perdana, Federal Territory of Putrajaya, Putrajaya, Malaysia. vijay@hygieiainnovation.com.
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Govindasamy
Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
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Abu Kasim
D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003731:Dental Caries; D003782:Dental Pulp / Q000166:cytology*; D059290:Dopaminergic Neurons / Q000502:physiology*; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D012038:Regeneration
gene expression; mesenchymal stem cells; neuro-ectoderm; neuronal lineage cells