Mesenchymal stem cells coated with synthetic bone-targeting polymers enhance osteoporotic bone fracture regeneration

Abstract

Osteoporosis is a progressive skeletal disease characterized by reduced bone density leading to bone fragility and an elevated risk of bone fractures. In osteoporotic conditions, decrease in bone density happens due to the augmented osteoclastic activity and the reduced number of osteoblast progenitor cells (mesenchymal stem cells, MSCs). We investigated a new method of cell therapy with membrane-engineered MSCs to restore the osteoblast progenitor pool and to inhibit osteoclastic activity in the fractured osteoporotic bones. The primary active sites of the polymer are the N-hydroxysuccinimide and bisphosphonate groups that allow the polymer to covalently bind to the MSCs’ plasma membrane, target hydroxyapatite molecules on the bone surface and inhibit osteolysis. The therapeutic utility of the membrane-engineered MSCs was investigated in female rats with induced estrogen-dependent osteoporosis and ulnar fractures. The analysis of the bone density dynamics showed a 27.4% and 21.5% increase in bone density at 4 and 24 weeks after the osteotomy of the ulna in animals that received four transplantations of polymer-modified MSCs. The results of the intravital observations were confirmed by the post-mortem analysis of histological slices of the fracture zones. Therefore, this combined approach that involves polymer and cell transplantation shows promise and warrants further bio-safety and clinical exploration.