PMID- 17827264
OWN - NLM
STAT- MEDLINE
DCOM- 20080131
LR  - 20220318
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 293
IP  - 6
DP  - 2007 Dec
TI  - Combined transmyocardial revascularization and cell-based angiogenic gene therapy 
      increases transplanted cell survival.
PG  - H3311-6
AB  - We hypothesized that pretreatment of an infarcted heart by mechanical 
      transmyocardial revascularization (TMR) before transplantation of bone marrow 
      cells (BMCs) or BMC-expressing angiogenic growth factors would increase 
      transplanted BMC survival and enhance myocardial repair. Female Lewis rats 
      underwent coronary ligation 3 wk before creation of 10 needle TMR channels (3 
      groups) or no TMR (3 groups), followed by transplantation of 3 x 10(6) male donor 
      BMCs, BMC transfected with vascular endothelial growth factor (VEGF), basic 
      fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1) (BMC + 
      VBI), or medium alone. At 1, 3, and 7 days, we evaluated transplanted cell 
      survival, vascular densities, and left ventricular (LV) function (N = 4 per group 
      x 6 groups x 3 time points). At 3 days, vascular densities in the scar were 
      increased by TMR + BMC + VBI and by BMC + VBI (P < 0.05), and at 7 days, vascular 
      densities were greatest in rats receiving TMR + BMC + VBI (P < 0.05). 
      Transplanted cell survival at 3 and 7 days was increased by TMR and by BMC + VBI. 
      Combined therapy with TMR + BMC + VBI resulted in the greatest cell survival at 3 
      days (P < 0.05) versus BMC. After 7 days, LV ejection fraction (LVEF) was lowest 
      in rats receiving neither BMC nor TMR and greatest in rats receiving TMR + BMC + 
      VBI (P = 0.004). We concluded that mechanical pretreatment of infarcted 
      myocardium by TMR enhances the effect of subsequent cell-based gene therapy on 
      transplanted cell survival, angiogenesis, and LV function. Scar pretreatment with 
      TMR combined with cell-based multigene therapy may maximize myocardial repair.
FAU - Spiegelstein, Dan
AU  - Spiegelstein D
AD  - Division of Cardiovascular Surgery, Toronto General Hospital, University Health 
      Network, 200 Elizabeth Street, Toronto, Ontario, Canada.
FAU - Kim, Christopher
AU  - Kim C
FAU - Zhang, Yaoguang
AU  - Zhang Y
FAU - Li, Guangming
AU  - Li G
FAU - Weisel, Richard D
AU  - Weisel RD
FAU - Li, Ren-Ke
AU  - Li RK
FAU - Yau, Terrence M
AU  - Yau TM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070907
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Angiogenic Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Angiogenic Proteins/genetics/*metabolism
MH  - Animals
MH  - Bone Marrow Cells/*metabolism
MH  - *Bone Marrow Transplantation
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Combined Modality Therapy
MH  - Coronary Vessels/*metabolism/pathology/physiopathology/surgery
MH  - Disease Models, Animal
MH  - Female
MH  - Fibroblast Growth Factor 2/metabolism
MH  - Genetic Therapy/*methods
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Ligation
MH  - Male
MH  - Myocardial 
      Infarction/genetics/metabolism/pathology/physiopathology/surgery/*therapy
MH  - Myocardial Revascularization/*methods
MH  - Myocardium/*metabolism/pathology
MH  - Neovascularization, Physiologic
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Stress, Mechanical
MH  - Stroke Volume
MH  - Time Factors
MH  - Transfection
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - Ventricular Function, Left
EDAT- 2007/09/11 09:00
MHDA- 2008/02/01 09:00
CRDT- 2007/09/11 09:00
PHST- 2007/09/11 09:00 [pubmed]
PHST- 2008/02/01 09:00 [medline]
PHST- 2007/09/11 09:00 [entrez]
AID - 00178.2007 [pii]
AID - 10.1152/ajpheart.00178.2007 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3311-6. doi: 
      10.1152/ajpheart.00178.2007. Epub 2007 Sep 7.