Abstract
Background
Osteoporosis and bone fractures lead to immobility, chronic pain and high patient care costs. Mesenchymal stem cells (MSCs) from postmenopausal women have a slower growth rate and osteogenic differentiation ability causing lower bone density and reduced fracture healing capacity compared to MSCs from premenopausal women. Cellular movement and relocalisation are necessary for many physiologic properties. Local MSCs from injured tissues and circulating MSCs are involved in fracture healing. Cytokines and chemokines such as SDF-1 and its receptor CXCR4 play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. This study investigated the effect of CXCR4 over-expression on the migration of MSCs from ovariectomised, normal and young rats.
Methods
MSCs were harvested from femora of young, normal and OVX rats, genetically modified to over-express CXCR4and put in a Boyden chamber to establish their migration towards SDF-1. This was compared to the non-transfected stem cells.
Results
MSCs from OVX rats migrate less towards SDF1 compared to MSCs from normal and juvenile rats. When the MSCs were differentiated to osteoblasts their migration towards SDF1 reduced as well and this was not enhanced by over-expression of CXCR4. Cell transfected with CXCR4 migrated more towards SDF-1 compared to non-transfected cells irrespective of whether these cells were from OVX, young or normal rats.
Conclusions
MSCs migration is impaired by age and osteoporosis explaining the significant reduction in bone formation in osteoporotic patients. The migration of stem cells can be ameliorated by up regulating the CXCR4 levels which could possibly enhance fracture healing in osteoporotic patients.
Level of Evidence
IIb
