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ReNCell VM conditioned medium enhances the induction of dental pulp stem cells into dopaminergic like cells

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Abstract

Among the debilitating diseases, neurological related diseases are the most challenging ones to be treated using cell replacement therapies. Recently, dental pulp stem cells (SHED) were found to be most suitable cell choice for neurological related diseases as evidenced with many preclinical studies. To enhance the neurological potential of SHED, we recapitulated one of the pharmacological therapeutic tools in cell replacement treatment, we pre-conditioned dental pulp stem cells (SHED) with culture medium of ReNCell VM, an immortalized neuron progenitor cell, prior to neurogenesis induction and investigated whether this practice enhances their neurogenesis potential especially towards dopaminergic neurons. We hypothesed that the integration of pharmacological practices such as co-administration of various drugs, a wide range of doses and duration as well as pre-conditioning into cell replacement may enhance the efficacy of stem cell therapy. In particular, pre-conditioning is shown to be involved in the protective effect from some membrano-tropic drugs, thereby improving the resistance of cell structures and homing capabilities. We found that cells pre-treated with ReNCell VM conditioned medium displayed bipolar structures with extensive branches resembling putative dopaminergic neurons as compared to non-treated cells. Furthermore, many neuronal related markers such as NES, NR4A2, MSI1, and TH were highly expressed (fold changes > 2; p < 0.05) in pre-treated cells. Similar observations were detected at the protein level. The results demonstrate for the first time that SHED pre-conditioning enhances neurological potential and we suggest that cells should be primed to their respective environment prior to transplantation.

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Acknowledgments

This work is part of research collaboration between Hygieia Innovation and the Faculty of Dentistry, University of Malaya. This work is supported by the University of Malaya, High Impact Research Grant, Ministry of Higher Education, Malaysia (Grant No. UM.C/HIR/MOHE/DENT/01).

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Authors declared no conflict of interest.

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Authors and Affiliations

  1. cGMP-Compliant Stem Cell Laboratory, Hygieia Innovation Sdn. Bhd, Lot 1G-2G, Lanai Complex No. 2, Persiaran Seri Perdana, Precinct 10, 62250, Federal Territory of Putrajaya, Malaysia

    Nareshwaran Gnanasegaran & Vijayendran Govindasamy

  2. Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia

    Nareshwaran Gnanasegaran & Noor Hayaty Abu Kasim

  3. Department of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia

    Sabri Musa

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  1. Nareshwaran Gnanasegaran
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  2. Vijayendran Govindasamy
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  3. Sabri Musa
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  4. Noor Hayaty Abu Kasim
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Correspondence to Vijayendran Govindasamy.

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Gnanasegaran, N., Govindasamy, V., Musa, S. et al. ReNCell VM conditioned medium enhances the induction of dental pulp stem cells into dopaminergic like cells. Cytotechnology 68, 343–353 (2016). https://doi.org/10.1007/s10616-014-9787-z

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  • DOI: https://doi.org/10.1007/s10616-014-9787-z

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