Periosteum progenitors could stimulate bone regeneration in aged murine bone defect model

Area of Science:

• Stem cell biology
• Regenerative medicine
• Skeletal biology

Background:

• Periosteal stem cells are crucial for bone regeneration but decrease with age.
• The role of Prx1-positive cells in age-related decline in bone healing is not fully understood.

Purpose of the Study:

• To investigate the potential of Prx1-positive cells to stimulate bone regeneration in aged mice.
• To determine the contribution of Prx1-positive cells to fracture healing across different age groups.

Main Methods:

• Utilized Prx1CreER-GFP; Rosa26tdTomato mice to track Prx1-positive cell participation in fracture healing.
• Analyzed Prx1-positive cell distribution in aged mice using Prx1CreER-GFP mice.
• Created bone defect models in aged mice and treated with hydrogel, Prx1-negative mesenchymal stem cells, or Prx1-positive cells.
• Employed H&E staining, micro-computed tomography, and mechanical testing to evaluate bone healing.

Main Results:

• Prx1-positive cells contribute to bone regeneration, particularly in younger individuals.
• The number of Prx1-positive cells significantly decreases with advancing age.
• Transplantation of Prx1-positive cells markedly improved bone regeneration in a murine bone defect model.
• Prx1-positive cells demonstrated superior osteogenic differentiation compared to Prx1-negative mesenchymal stem cells.

Conclusions:

• The decline in Prx1-positive cell quantity likely contributes to reduced bone regeneration capacity in aged mice.
• Transplantation of Prx1-positive cells offers a promising therapeutic strategy to enhance bone regeneration at defect sites, even in aging populations.