Feasibility of dental stem cells in clinical applications and technical advances

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The first human study using dental pulp stem/stromal cells in mandible bone made significant impact in the field of regenerative medicine (d’Aquino et al. 2009). This study laid the foundation for subsequent attempts of dental stem cell research from bench to bedside. Till date, however, only two clinical trials have been carried out using dental stem cells to our knowledge. This is perhaps due to their relative novelty, infancy of the research area and also insufficient preclinical evidence to enable the approval of human testing or clinical protocols. One of the human clinical trials conducted using autologous PDL stem cells transplantation showed therapeutic improvement for the periodontal defects without any adverse effects (Feng et al. 2010; https://clinicaltrials.gov/ct2/show/NCT01357785). Studies have shown that DPSCs are capable of differentiating into fully functional neuronal cells (Iohara et al. 2006), odontoblast (Sakai et al. 2010), endothelium (Sakai et al. 2010), hepatocytes (Ishkitiew et al. 2010) and pancreatic cells (Govindasamy et al. 2011). Along with these some pre-clinical studies showed remarkable outcomes using DPSCs in the area of acute myocardial infarction and neurodegenerative disease (Gandia et al. 2008; Wang et al. 2009).

Recent reports have also revealed the potential application of DPSCs for corneal stromal regeneration with strong evidence provided with in vivo animal studies (Syed-Picard et al. 2015). In regard to technical advances, investigators attempt to develop a novel protocol to induce subsets of DPSCs to form ‘mobilized DPSCs’ using granulocyte-colony stimulating factor (G-CSF) (Nakashima and Iohara 2014). This enables safe and efficient transplantation of pulp stem cells, serving as a prologue for the initiation of clinical trials.

In addition, a recent study outlined the design of medicinal manufacturing approaches for the production of human DPSCs, which follows current international guidelines for ex vivo expanded cells (Ducret et al. 2015). They provided an easy, safe, quick and cost effective protocol for the production of clinical grade mesenchymal pulp cells that maintain their stem cell properties and multipotent differentiation potentials under xeno-free conditions. Thus, as technologies advance in the future it is not surprising if DPSCs emerge as a potent surrogate of traditionally used BM-MSCs for human clinical trials. This paradigm shift would make more treatment options available by use of tailor-made stem cells for debilitating diseases, with anticipation to achieve maximum efficacy in regenerative medicine. Figure 3 depicts a model of dental derived stem cell usage and its differentiation studies performed under in vivo and in vitro models.