Hypoxia-driven Dental Pulp Stem Cells as a Promising Strategy for Tissue Regeneration

: Hypoxia is a common hallmark in both physiological and pathological states. The adaptation to hypoxia is a key cellular event in the development and differentiation of stem cells, as well as in pathological conditions such as ischemia. The hypoxic microenvironment, culture conditions, and reactive oxygen species (ROS) scavengers have all been shown to enhance the proliferation, anti-aging properties, immunomodulatory capabilities, differentiation potential, and regenerative and therapeutic potential of dental pulp stem cells (DPSCs). However, severe and persistent hypoxia can be detrimental to the survival and tissue regeneration of DPSCs. Therefore, hypoxic preconditioning of DPSCs and applying oxygen-releasing materials to mitigate extreme hypoxia can enhance the regenerative and therapeutic potential in damaged organisms. This article provides a comprehensive review of the influence of the hypoxic microenvironment on the biological characteristics of dental pulp stem cells (DPSCs). It also presents a summary of the recent research advances in DPSCs regarding tissue regeneration, particularly focusing on the utilization of hypoxic preconditioning. Additionally, this review highlights the diverse biological effects of hypoxia on tissue regeneration and proposes promising novel therapeutic strategies.