Stem Cells from Human Exfoliated Deciduous Teeth Ameliorate Autistic-Like Behaviors of SHANK3 Mutant Beagle Dogs

Mesenchymal stem cell-based therapy has emerged as a great potential approach to treat individuals with autism spectrum disorders (ASD), a group of developmental disabilities characterized by impairments in social interaction and communication. Stem cells from human exfoliated deciduous teeth (SHED), holding earlier developing characteristics, have immune-modulatory and anti-inflammatory properties. To investigate whether SHED transplantation can rescue autistic-like symptoms in SHANK3 mutant beagle dogs, 12 SHANK3 mutant beagle dogs were randomly assigned into 2 groups according to their behavior evaluated by social interaction tests. Six mutant dogs received 6 intravenous infusions of SHED and were followed up for 3 months by testing social interaction and inflammatory cytokine levels. We found that infusion of SHED significantly improved impaired social novel preference of SHANK3 mutant beagle dogs at 1- and 3-month follow-ups. Social intimacies (following, sniffing, and licking) between mutant beagle dogs and human experimenters were partly improved. Stressed tail posture, indicating social stress, was also significantly alleviated. In addition, we showed that the levels of serum interferon-gamma and interleukin-10 were notably increased and decreased, respectively, in SHANK3 mutant beagle dogs. Infusion of SHED was able to rescue altered interferon-gamma and interleukin-10 levels. We failed to observe any serious adverse events after infusion of SHED. In summary, SHED transplantation may be a safe and effective therapy for ASD. The correction in the levels of serum interferon-gamma and interleukin-10 may serve as an index to predict autistic severity and therapeutic outcomes.