Stem Cells From Human Exfoliated Deciduous Teeth-Conditioned Medium (SHED-CM) is a Promising Treatment for Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterized by the loss of upper and lower motor neurons, for which an effective treatment has yet to be developed. Previous reports have shown that excessive oxidative stress, related to mitochondrial dysfunction and the accumulation of misfolding protein, contributes to ALS pathology. In terms of treatment, it remains necessary to identify effective medicines for multiple therapeutic targets and have additive effects against several disorders. In this study, we investigated stem cells from human exfoliated deciduous teeth (SHED), which release many factors, such as neurotrophic factors and cytokines, and are applied to treat neurological diseases. Specifically, we examined whether SHED-conditioned medium (CM), i.e., the serum-free culture supernatant of SHED, reduced mutant SOD1-induced intracellular aggregates and neurotoxicity. We found that SHED-CM significantly suppressed the mutant SOD1-induced intracellular aggregates and neurotoxicity. The neuroprotective effects of SHED-CM are partly related to heat shock protein and the activation of insulin-like growth factor-1 receptor. SHED-CM also had a protective effect on induced pluripotent stem cell-derived motor neurons. Moreover, SHED-CM was effective against not only familial ALS but also sporadic ALS. Overall, these results suggest that SHED-CM could be a promising treatment for slowing the progression of ALS.

Characteristics and Therapeutic Potential of Dental Pulp Stem Cells on Neurodegenerative Diseases.

To evaluate the therapeutic potential of stem cells for neurodegenerative diseases, emphasis should be placed on clarifying the characteristics of the various types of stem cells. Among stem cells, dental pulp stem cells (DPSCs) are a cell population that is rich in cell proliferation and multipotency. It has been reported that transplantation of DPSCs has protective effects against models of neurodegenerative diseases. The protective effects are not only through differentiation into the target cell type for the disease but are also related to trophic factors released from DPSCs. Recently, it has been reported that serum-free culture supernatant of dental pulp stem cell-conditioned medium (DPCM) contains various trophic factors and cytokines and that DPCM is effective for models of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS). Moreover, the use of stem cells from human exfoliated deciduous teeth (SHEDs) has been considered. SHEDs are derived from deciduous teeth that have been disposed of as medical waste. SHEDs have higher differentiation capacity and proliferation ability than DPSCs. In addition, the serum-free culture supernatant of SHEDs (SHED-CM) contains more trophic factors, cytokines, and biometals than DPCM and also promotes neuroprotection. The neuroprotective effect of DPSCs, including those from deciduous teeth, will be used as the seeds of therapeutic drugs for neurodegenerative diseases. SHEDs will be used for further cell therapy of neurodegenerative diseases in the future. In this paper, we focused on the characteristics of DPSCs and their potential for neurodegenerative diseases.