Transplanted MSCs Promote Vascularized Bone Regeneration Via Intracellular Zn2+ Transportation

Mesenchymal stem cell (MSC) therapy has shown obvious advantages in promoting bone tissue regeneration. However, the regulatory mechanism of MSC therapy promoting bone tissue repair is actually unclear. This study aims to explore the metal ion exchange between mitochondrial and cytoplasmic pools in hypoxia microenvironment, and its regulatory effect in MSC therapy. Mice skull defect model was used in vivo to investigate the effectiveness of MSC therapy on bone defect healing. Protein array was used in vitro to explore the key regulatory factors of transplanted stem cells, and further investigations were performed to explore the mechanism and influence of hypoxia-induced intracellular ion transport in BMSCs. In vivo transplantation of BMSC sheet promotes the regeneration of vascularized bone. Protein array confirmed that MMP-10 is the key regulatory protein of transplanted BMSCs. Hypoxia induced mitochondrial permeability increase and cytoplasmic Zn2+ transport, and cytoplasmic Zn2+ accumulation is a key factor in the activation of JAK1/STAT1/MMP-10. This study reported for the first time the regulatory mechanism and influence significance of zinc ion transport in cytoplasm of hypoxia-induced transplanted stem cells, which further elucidates the treatment mechanisms of transplanted MSCs, and provides strategies for the design and development of stem cell-based biomaterials.