title: Stem cell therapy in the aging hearts of Fisher 344 rats: synergistic effects on myogenesis and angiogenesis.
abstract: OBJECTIVE
  Advanced age is a major risk factor for ventricular dysfunction and reduction of cardiac reserve. Finding novel approaches to prevent and attenuate heart dysfunction associated with advanced age is a major therapeutic challenge. The present study was designed to test whether engrafted embryonic stem cells could improve myocardial function in aging hearts.
  
  
  METHODS
  Cultured mouse embryonic stem cells used for cell therapy were transfected with green fluorescent protein. Aging rats in the cell-treated group received intramyocardial injection of embryonic stem cells. Hemodynamic measurement, myocyte counting, and evaluation of blood flow were performed 6 weeks after cell transplantation.
  
  
  RESULTS
  Embryonic stem cell therapy partially improved cardiac reserve, as reflected by the in vivo response to isoproterenol (INN: isoprenaline) stimulation in aging hearts 6 weeks after cell implantation. The functional benefits from engrafted embryonic stem cells were associated with increased myocyte numbers and enhanced left ventricular blood perfusion in the aging heart. The characteristic phenotype of engrafted embryonic stem cells was identified in the transplanted heart on the basis of green fluorescent protein-positive spots that were further demonstrated to differentiate into cardiac tissue with positive staining for cardiac alpha-myosin heavy chain.
  
  
  CONCLUSIONS
  Regenerating cardiomyocytes and increasing regional blood perfusion in the aging heart after embryonic stem cell transplantation synergistically resulted in improvement of cardiac function. Embryonic stem cell transplantation might hold significant clinical potential in attenuating the progressive decrease of cardiac function associated with advanced aging.
authors.affiliation: Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Jiang-Yong
authors.initials: JY
authors.lastname: Min
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Sohail
authors.initials: S
authors.lastname: Malek
authors.forename: Achim
authors.initials: A
authors.lastname: Meissner
authors.forename: Meixiang
authors.initials: M
authors.lastname: Xiang
authors.forename: Qinen
authors.initials: Q
authors.lastname: Ke
authors.forename: Xin
authors.initials: X
authors.lastname: Feng
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nakayama
authors.forename: Emel
authors.initials: E
authors.lastname: Kaplan
authors.forename: James P
authors.initials: JP
authors.lastname: Morgan
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D015552:Injections, Intralesional; D008297:Male; D023421:Models, Animal; D024510:Muscle Development / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods*