Key result
Young Sca-1+ cell reconstitution drives a ~3-fold increase in cardiac PDGFRβ+ cells, improving post-MI function.
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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.
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Li et al. (2017) studied Myocardial infarction in aged mice. Bone marrow reconstitution with young Sca-1+ stem cells vs. Young Sca-1- bone marrow cells or old bone marrow cells was evaluated on Cardiac tissue regeneration, ventricular function after MI, and PDGFRβ co-expression in aged myocardium (3-fold increase in BM-derived cells co-expressing PDGFRβ). Young bone marrow Sca-1+ stem cell reconstitution increased cardiac PDGFRβ+ BM-derived cells 3-fold and improved post-MI ventricular function in aged mice.
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