Young Bone-Marrow Sca-1(+) Stem Cells Rejuvenate the Aged Heart and Improve Function after Injury through PDGFRβ-Akt pathway

Bone marrow (BM) reconstitution with young BM cells in aged recipients restores the functionality of cardiac resident BM-derived progenitors. This study investigated the cell type primarily responsible for this effect. We reconstituted old mice with BM cells from young or old mice and found that the number of stem cell antigen 1 (Sca-1) cells homing to the heart was significantly greater in young than old chimeras. We then reconstituted old mice with young BM Sca-1(+) or Sca-1(−) cells. We found that Sca-1 cells repopulated the recipient BM and homed to the heart. The number of BM-derived cells in the aged myocardium co-expressing PDGFRβ was 3 times greater in Sca-1(+) than Sca-1(−) chimeric mice. Sca-1(+) chimeras had more active cell proliferation in the infarcted heart and improved ventricular function after MI. The improved regeneration involved activation of the PDGFRβ/Akt/p27(Kip1) pathway. Sca-1(+) stem cells rejuvenated cardiac tissue in aged mice. Restoration of the Sca-1(+) subset of stem cells by BM reconstitution improved cardiac tissue regeneration after injury in aged mice.