PMID- 19929464
OWN - NLM
STAT- MEDLINE
DCOM- 20100121
LR  - 20220318
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Linking)
VI  - 11
IP  - 8
DP  - 2009
TI  - Long-term benefit of intracardiac delivery of autologous 
      granulocyte-colony-stimulating factor-mobilized blood CD34+ cells containing 
      cardiac progenitors on regional heart structure and function after myocardial 
      infarct.
PG  - 1002-15
LID - 10.3109/14653240903164963 [doi]
AB  - BACKGROUND AIMS: Starting from experimental data proposing hematopoietic stem 
      cells as candidates for cardiac repair, we postulated that human peripheral blood 
      (PB) CD34+ cells mobilized by hematopoietic growth-factor (G-CSF) would contain 
      cell subpopulations capable of regenerating post-ischemic myocardial damages. 
      METHODS: In a phase I clinical assay enrolling seven patients with acute 
      myocardial infarct, we directly delivered to the injured myocardium autologous PB 
      CD34+ cells previously mobilized by G-CSF, collected by leukapheresis and 
      purified by immunoselection. In parallel, we looked for the eventual presence of 
      cardiomyocytic and endothelial progenitor cells in leukapheresis products of 
      these patients and controls, using flow cytometry, reverse 
      transcription-quantitative (RTQ)-polymerase chain reaction (PCR), cell cultures 
      and immunofluorescence analyzes. RESULTS: The whole clinical process was feasible 
      and safe. All patients were alive at an average follow-up of 49 months (range 
      24-76 months). Improvement of heart function parameters became obvious from the 
      third month following cell reinjection. Left ventricular ejection fraction values 
      progressively and dramatically increased with time, associated with PetScan 
      demonstration of myocardial structure regeneration and revascularization and New 
      York Heart Association (NYHA) grade improvement. Furthermore, we identified PB 
      CD34+ cell subpopulations expressing characteristics of both immature and mature 
      endothelial and cardiomyocyte progenitor cells. In vitro CD34+ cell cultures on a 
      specific medium induced development of adherent cells featuring morphologies, 
      gene expression and immunocytochemistry characteristics of endothelial and 
      cardiac muscle cells. CONCLUSIONS: Mobilized CD34+ cells contain stem cells 
      committed along endothelial and cardiac differentiation pathways, which could 
      play a key role in a proposed two-phase mechanism of myocardial regeneration 
      after direct intracardiac delivery, probably being responsible for the long-term 
      clinical benefit observed.
FAU - Pasquet, Stephanie
AU  - Pasquet S
AD  - Institut de Recherche en Hematologie et Transplantation (IRHT), Mulhouse, France.
FAU - Sovalat, Hanna
AU  - Sovalat H
FAU - Henon, Philippe
AU  - Henon P
FAU - Bischoff, Nicolas
AU  - Bischoff N
FAU - Arkam, Yazid
AU  - Arkam Y
FAU - Ojeda-Uribe, Mario
AU  - Ojeda-Uribe M
FAU - Bouar, Ronan le
AU  - Bouar Rl
FAU - Rimelen, Valerie
AU  - Rimelen V
FAU - Brink, Ingo
AU  - Brink I
FAU - Dallemand, Robert
AU  - Dallemand R
FAU - Monassier, Jean-Pierre
AU  - Monassier JP
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - 0 (Antigens, CD34)
RN  - 0 (Muscle Proteins)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigens, CD34/*metabolism
MH  - Cell Adhesion/drug effects
MH  - Cell Dedifferentiation/drug effects
MH  - Cells, Cultured
MH  - Drug Administration Routes
MH  - Endothelial Cells/cytology/metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Regulation/drug effects
MH  - Granulocyte Colony-Stimulating Factor/*administration & 
      dosage/pharmacology/*therapeutic use
MH  - *Hematopoietic Stem Cell Mobilization
MH  - Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Muscle Proteins/genetics/metabolism
MH  - Myocardial Infarction/drug therapy/pathology/*physiopathology
MH  - Myocardium/*pathology
MH  - Stem Cells/*cytology/drug effects/metabolism
MH  - Stroke Volume/drug effects/physiology
MH  - Time Factors
MH  - Transplantation, Autologous
MH  - Treatment Outcome
EDAT- 2009/11/26 06:00
MHDA- 2010/01/22 06:00
CRDT- 2009/11/26 06:00
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/11/26 06:00 [pubmed]
PHST- 2010/01/22 06:00 [medline]
AID - S1465-3249(09)70348-2 [pii]
AID - 10.3109/14653240903164963 [doi]
PST - ppublish
SO  - Cytotherapy. 2009;11(8):1002-15. doi: 10.3109/14653240903164963.