The Effects of Hypoxia-Preconditioned Dental Stem Cell-Derived Secretome on Tissue Regeneration

Mesenchymal stroma cells derived from oral tissues are known as dental stem cells (DSCs). Owing to their unique therapeutic niche and clinical accessibility, DSCs serve as a promising treatment option for bone defects and oral tissue regeneration. DSCs exist in a hypoxic microenvironment in vivo, which is far lower than the current 20% oxygen concentration used in in vitro culture. It has been widely reported that the application of an oxygen concentration less than 5% in the culture of DSCs is beneficial for preserving stemness and promoting proliferation, migration, and paracrine activity. The paracrine function of DSCs involves the secretome, which includes conditioned media (CM) and soluble bioactive molecules, as well as extracellular vesicles extracted from CM. Hypoxia can play a role in immunomodulation and angiogenesis by altering the protein or nucleic acid components in the secretory group, which enhances the therapeutic potential of DSCs. This review summarizes the biological characteristics of DSCs, the influence of hypoxia on DSCs, the impact of hypoxia on the secretory group of DSCs, and the latest progress on the use of DSCs secretory group in tissue regeneration based on hypoxia pretreatment. We highlighted the multifunctional biological effect of hypoxia culture on tissue regeneration and provided a summary of the current mechanism of hypoxia in the pretreatment of DSCs. Impact Statement Dental stem cells (DSCs) are mesenchymal stroma cells obtained from oral tissues. It has been demonstrated that hypoxia preconditioning, which mimics the in vivo living conditions of dental stem cells, helps preserve the stemness of stem cells and encourages the proliferation, migration, homing, differentiation, and paracrine activity. The healing of tissue has been greatly aided by the therapy administered by the secretory group of DSCs. It will be beneficial to the development of cell-free therapy and enhance clinical application to investigate the influence of hypoxia on DSCs, its molecular mechanism, and the therapeutic use of hypoxia secretory group in illnesses.