title: Identification of small juvenile stem cells in aged bone marrow and their therapeutic potential for repair of the ischemic heart.
abstract: Stem cell-mediated cardiac regeneration is impaired with age. In this study, we identified a novel subpopulation of small juvenile stem cells (SJSCs) isolated from aged bone marrow-derived stem cells (BMSCs) with high proliferation and differentiation potential. SJSCs expressed mesenchymal stem cell markers, CD29(+)/CD44(+)/CD59(+)/CD90(+), but were negative for CD45(-)/CD117(-) as examined by flow cytometry analysis. SJSCs showed higher proliferation, colony formation, and differentiation abilities compared with BMSCs. We also observed that SJSCs significantly expressed cardiac lineage markers (Gata-4 and myocyte-specific enhancer factor 2C) and pluripotency markers (octamer-binding transcription factor 4, sex-determining region Y box 2, stage-specific embryonic antigen 1, and Nanog) as well as antiaging factors such as telomerase reverse transcriptase and sirtuin 1. Interestingly, SJSCs either from young or aged animals showed significantly longer telomere length as well as lower senescence-associated β-galactosidase expression, suggesting that SJSCs possess antiaging properties, whereas aged BMSCs have limited potential for proliferation and differentiation. Furthermore, transplantation of aged SJSCs into the infarcted rat heart significantly reduced the infarction size and improved left ventricular function, whereas transplantation of aged BMSCs was less effective. Moreover, neovascularization as well as cardiomyogenic differentiation in the peri-infarcted area were significantly increased in the SJSC-transplanted group compared with the BMSC-transplated group, as evaluated by immunohistochemical analysis. Taken together, these findings demonstrate that SJSCs possess characteristics of antiaging, pluripotency, and high proliferation and differentiation rates, and, therefore, these cells offer great therapeutic potential for repair of the injured myocardium.
authors.affiliation: Department of Pathology and Lab of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio.
authors.forename: Koichi
authors.initials: K
authors.lastname: Igura
authors.forename: Motoi
authors.initials: M
authors.lastname: Okada
authors.forename: Ha Won
authors.initials: HW
authors.lastname: Kim
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D016922:Cellular Senescence; D004195:Disease Models, Animal; D005260:Female; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function; D012038:Regeneration; D016615:Telomere / Q000378:metabolism; D059505:Telomere Homeostasis; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers
keywords: antiaging; cardiac repair; small juvenile stem cell