title: Young Bone-Marrow Sca-1+Stem Cells Rejuvenate the Aged Heart and Improve Function after Injury through PDGFRβ-Akt pathway.
abstract: 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/p27Kip1pathway. 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.
authors.affiliation: Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.|Department of Cardiology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Cardiovascular Disease, Guangzhou, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Zhengbo
authors.initials: Z
authors.lastname: Shao
authors.affiliation: 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.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Du
authors.affiliation: Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.|Division of Cardiac Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Weisel
authors.affiliation: Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.|Division of Cardiac Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.
authors.forename: Ren-Ke
authors.initials: RK
authors.lastname: Li
mesh_terms: D000367:Age Factors; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D018183:Transplantation Chimera
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt