title: Repeated Administrations of Cardiac Progenitor Cells Are Markedly More Effective Than a Single Administration: A New Paradigm in Cell Therapy.
abstract: BACKGROUND
  The effects of c-kit(POS) cardiac progenitor cells (CPCs, and adult cell therapy in general) on left ventricular (LV) function have been regarded as modest or inconsistent.
  
  
  OBJECTIVE
  To determine whether 3 CPC infusions have greater efficacy than 1 infusion.
  
  
  RESULTS
  Rats with a 30-day-old myocardial infarction received 1 or 3 CPC infusions into the LV cavity, 35 days apart. Compared with vehicle-treated rats, the single-dose group exhibited improved LV function after the first infusion (consisting of CPCs) but not after the second and third (vehicle). In contrast, in the multiple-dose group, regional and global LV function improved by a similar degree after each CPC infusion, resulting in greater cumulative effects. For example, the total increase in LV ejection fraction was approximately triple in the multiple-dose group versus the single-dose group (P<0.01). The multiple-dose group also exhibited more viable tissue and less scar, less collagen in the risk and noninfarcted regions, and greater myocyte density in the risk region.
  
  
  CONCLUSIONS
  This is the first demonstration that repeated CPC administrations are markedly more effective than a single administration. The concept that the full effects of CPCs require repeated doses has significant implications for both preclinical and clinical studies; it suggests that the benefits of cell therapy may be underestimated or even overlooked if they are measured after a single dose, and that repeated administrations are necessary to evaluate the effectiveness of a cell product properly. In addition, we describe a new method that enables studies of repeated cell administrations in rodents.
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Tokita
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Xian-Liang
authors.initials: XL
authors.lastname: Tang
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Qianhong
authors.initials: Q
authors.lastname: Li
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wysoczynski
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Kyung U
authors.initials: KU
authors.lastname: Hong
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Wen-Jian
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Greg
authors.initials: G
authors.lastname: Hunt
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Ou
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Heather
authors.initials: H
authors.lastname: Stowers
authors.affiliation: From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY. rbolli@louisville.edu.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods / Q000639:trends; D005260:Female; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D013234:Stem Cells / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology
keywords: cardiac progenitor cells; cell therapy; collagen; left ventricular function; myocardial infarction; reperfusion injury; ventricular remodeling