PMID- 23997098 OWN - NLM STAT- MEDLINE DCOM- 20131227 LR - 20211021 IS - 1522-1539 (Electronic) IS - 0363-6135 (Print) IS - 0363-6135 (Linking) VI - 305 IP - 9 DP - 2013 Nov 1 TI - Identification of small juvenile stem cells in aged bone marrow and their therapeutic potential for repair of the ischemic heart. PG - H1354-62 LID - 10.1152/ajpheart.00379.2013 [doi] AB - 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 beta-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. FAU - Igura, Koichi AU - Igura K AD - Department of Pathology and Lab of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio. FAU - Okada, Motoi AU - Okada M FAU - Kim, Ha Won AU - Kim HW FAU - Ashraf, Muhammad AU - Ashraf M LA - eng GR - HL-087246/HL/NHLBI NIH HHS/United States GR - HL-095375/HL/NHLBI NIH HHS/United States GR - R37-HL-074272/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130830 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - 0 (Biomarkers) SB - IM MH - Age Factors MH - Animals MH - Biomarkers/metabolism MH - *Bone Marrow Cells/metabolism MH - *Bone Marrow Transplantation MH - Cell Differentiation MH - Cell Lineage MH - Cell Proliferation MH - Cell Separation MH - Cells, Cultured MH - *Cellular Senescence MH - Disease Models, Animal MH - Female MH - Myocardial Infarction/metabolism/pathology/physiopathology/*surgery MH - Myocardium/metabolism/*pathology MH - Pluripotent Stem Cells/metabolism/*transplantation MH - Rats MH - Rats, Inbred F344 MH - Recovery of Function MH - *Regeneration MH - Telomere/metabolism MH - Telomere Homeostasis MH - Time Factors MH - Ventricular Function, Left PMC - PMC3840241 OTO - NOTNLM OT - antiaging OT - cardiac repair OT - small juvenile stem cell EDAT- 2013/09/03 06:00 MHDA- 2013/12/29 06:00 PMCR- 2014/11/01 CRDT- 2013/09/03 06:00 PHST- 2013/09/03 06:00 [entrez] PHST- 2013/09/03 06:00 [pubmed] PHST- 2013/12/29 06:00 [medline] PHST- 2014/11/01 00:00 [pmc-release] AID - ajpheart.00379.2013 [pii] AID - H-00379-2013 [pii] AID - 10.1152/ajpheart.00379.2013 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2013 Nov 1;305(9):H1354-62. doi: 10.1152/ajpheart.00379.2013. Epub 2013 Aug 30.