title: ReNCell VM conditioned medium enhances the induction of dental pulp stem cells into dopaminergic like cells.
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.
authors.affiliation: 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.|Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nareshwaran
authors.initials: N
authors.lastname: Gnanasegaran
authors.affiliation: 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. vijay07001@gmail.com.
authors.forename: Vijayendran
authors.initials: V
authors.lastname: Govindasamy
authors.affiliation: Department of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sabri
authors.initials: S
authors.lastname: Musa
authors.affiliation: Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Noor Hayaty
authors.initials: NH
authors.lastname: Abu Kasim
keywords: Dopamine acetyl-transferase; Mesenchymal stem cells; Neural progenitor cells; Neurogenesis; Tyrosine hydroxylase