Brief Report: Long-Term Functional Engraftment of Mesenchymal Progenitor Cells in a Mouse Model of Accelerated Aging§

Authors


  • Author contributions: L.S., T.B., J.-H.K., and Y.Z.: collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; K.P.E. and E.A.M.: collection and/or assembly of data and final approval of manuscript; Q.C.: collection and/or assembly of data, provision of study materials, and final approval of manuscript; K.D.H. and S.G.E.: data analysis and interpretation, manuscript writing, and final approval of manuscript; F.B.J.: collection and/or assembly of data, provision of study materials, data analysis and interpretation, manuscript writing, and final approval of manuscript; R.J.P.: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript. L.S. and T.A.B. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS November 29, 2012.

Abstract

Age-related osteoporosis is characterized by a decrease in bone-forming capacity mediated by defects in the number and function of osteoblasts. An important cellular mechanism that may in part explain osteoblast dysfunction that occurs with aging is senescence of mesenchymal progenitor cells (MPCs). In the telomere-based Wrn−/−Terc−/− model of accelerated aging, the osteoporotic phenotype of these mice is also associated with a major decline in MPC differentiation into osteoblasts. To investigate the role of MPC aging as a cell-autonomous mechanism in senile bone loss, transplantation of young wild-type whole bone marrow into Wrn−/−Terc−/− mutants was performed and the ability of engrafted cells to differentiate into cells of the osteoblast lineage was assessed. We found that whole bone marrow transplantation in Wrn−/−Terc−/− mice resulted in functional engraftment of MPCs up to 42 weeks, which was accompanied by a survival advantage as well as delays in microarchitectural features of skeletal aging. STEM CELLS2013;31:607–611

Ancillary