Typically, stress is considered a negative factor for an individual's health. But a new study at the University of Hong Kong (HKU) Dentistry suggests that ‘positive stress’ could have a positive impact on tooth stem cells.
The study showed that adaptive mechanisms in tooth stem cells induced by preconditioning to stress can boost tooth pulp tissue regeneration. Oxidative stress (caused by low oxygen environments) elicited a protective response making tooth cells less vulnerable to harm.
For dental pulp regeneration, stem cell-based therapeutics are widely being considered. However, due to the tooth root canal being surrounded by hard dental tissue and a limited blood supply this is a harsh environment for cells with low-oxygen and nutrients. One of the critical challenges facing this field of research is combating the low cell viability that these conditions create.
HKU’s team developed a protocol that genetically modified the cells to mimic a responsive state for low oxygen conditions which activated a protein that induces adaptive changes in the cells.
Dr Yuanyuan Han, a co-investigator of the team pointed out, "As this protein was reported to activate several key adaptive mechanisms, we wondered whether this phenomenon can be applied to improve cell survival following transplantation until a sufficient blood supply is achieved."
"In our study, we found that these cells activate a metabolic mechanism to produce energy under low oxygen conditions and scavenge harmful metabolites produced in stress conditions.” Dr Han. explained.
"Former research has revealed that our cells possess number of adaptive mechanisms for stress, which are regulated by several key genes encoded in our DNA that are normally inactive," said Dr Dr Waruna Dissanayaka, Assistant Professor in Oral Biosciences and leader of the research team. "If we can activate these genes, downstream expression of specific proteins can prime the cells less vulnerable to injury."
The team also worked with Dr Mohamad Koohi-Moghadam, Research Assistant Professor in Clinical Artificial Intelligence to determine which genes are activated or repressed during preconditioning. They plan to continue this work to identify which unregulated downstream proteins make the cells damage-resistant.
Waruna plans to utilise the research to identify potential drugs for clinical tissue regeneration and to develop strategies to enhance the therapeutic potential of tooth stem cells.
Read the study here: http://dx.doi.org/10.1177/00220345221091528