Angiogenic pretreatment improves the efficacy of cellular cardiomyoplasty performed with fetal cardiomyocyte implantation.
BACKGROUND
Cell implantation into areas of myocardial infarction (cellular cardiomyoplasty) may be limited in efficacy because of the lack of blood supply to these areas of myocardium, resulting in early loss of transplanted cells. We therefore tested the hypothesis that pretreatment of infarcted myocardium with angiogenic therapy, followed by cell transplant, would be more effective than the application of either strategy alone.


METHODS
Fischer 344 rats underwent left coronary artery ligation and injection of an adenovirus encoding VEGF 121, an empty expression cassette control vector, or saline solution. Capillary density in the infarcted region was determined in preliminary studies. Cardiomyocytes harvested from syngeneic Fischer rat fetuses were prelabeled and then injected directly into the infarct area 3 weeks after vector administration. Exercise treadmill testing was performed 2 weeks after cell transplantation, after which a cell viability index was calculated as the number of implanted (prelabeled) nuclei divided by the number of coadministered microspheres detected in sections of implanted myocardium.


RESULTS
Capillary density in the area of infarction was significantly greater in adenovirus encoding VEGF 121 compared with rats injected with saline solution (P =.001). The cell survival index was also greater in adenovirus encoding VEGF 121 compared with animals injected with empty expression cassette control or saline solution (P =.0045). Exercise tolerance was nearly doubled in animals receiving adenovirus encoding VEGF 121 3 weeks prior to cell implantation compared with animals receiving adenovirus encoding VEGF 121 or cells alone or those receiving adenovirus encoding VEGF 121 at the time of cell implantation (P <.001).


CONCLUSIONS
Pretreatment of an infarcted region of the heart with angiogenic mediators such as VEGF can enhance the efficacy of cellular cardiomyoplasty, presumably by creating a more favorable environment for the survival of transplanted cells.
Retuerto
Mauricio A
MA
Evanston Northwest Healthcare, IL 60201, USA.
Schalch
Paul
P
Patejunas
Gerald
G
Carbray
JoAnn
J
Liu
Naxin
N
Esser
Karyn
K
Crystal
Ronald G
RG
Rosengart
Todd K
TK
D000818:Animals; D018421:Cardiomyoplasty; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017690:Cell Transplantation; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D005318:Fetal Heart / Q000166:cytology*; D008297:Male; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000166:cytology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000637:transplantation* / Q000648:ultrastructure; D051381:Rats; D011916:Rats, Inbred F344; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D042461:Vascular Endothelial Growth Factor A