年轻的骨髓 Sca-1 干细胞通过 PDGFRβ-Akt 通路使衰老的心脏恢复活力，并在损伤后改善其功能。

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

机构信息

Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.

Research Institute, Second Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Sci Rep. 2017 Jan 31;7:41756. doi: 10.1038/srep41756.

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 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.

骨髓（BM）中年轻的 BM 细胞在老年受者中重建，恢复了心脏固有 BM 衍生祖细胞的功能。本研究探讨了主要负责这一效应的细胞类型。我们用来自年轻或年老小鼠的 BM 细胞重建老年小鼠，发现年轻嵌合体中向心脏归巢的干细胞抗原 1（Sca-1）细胞数量明显多于年老嵌合体。然后，我们用年轻的 BM Sca-1 或 Sca-1 细胞重建老年小鼠。我们发现 Sca-1 细胞重新填充了受者的 BM 并归巢到心脏。在 Sca-1 比 Sca-1 嵌合小鼠中，表达 PDGFRβ 的年龄相关心肌中 BM 来源细胞的数量增加了 3 倍。Sca-1 嵌合体在梗塞心脏中有更多的活跃细胞增殖，并且在 MI 后改善了心室功能。改善的再生涉及 PDGFRβ/Akt/p27 途径的激活。Sca-1 干细胞使老年小鼠的心脏组织年轻化。BM 重建恢复了 Sca-1 干细胞亚群，改善了老年小鼠损伤后的心脏组织再生。