Heterotopic bone formation derived from multipotent stromal cells is not inhibited in aged mice.

Abstract

Decreased bone formation with age is believed to arise, at least in part, because of the influence of the senescent microenvironment. In this context, it is unclear whether multipotent stromal cell (MSC)-based therapies would be effective for the treatment of bone diseases. With the use of a heterotopic bone formation model, we investigated whether MSC-derived osteogenesis is impaired in aged mice compared with young mice. We found that bone formation derived from MSCs is not reduced in aged mice. These results are supported by the unexpected finding that conditioned media collected from ionizing radiation-induced senescent MSCs can stimulate mineralization and delay osteoclastogenesis in vitro. Overall, our results suggest that impaired bone formation with age is mainly cell-autonomous and provide a rationale for the use of MSC-based therapies for the treatment of bone diseases in the elderly.