Can erythropoietin improve skeletal myoblast engraftment in infarcted myocardium?
The benefits of skeletal myoblast transplantation are limited by the high rate of early cell death which is partly of ischemic origin. We, therefore, assessed whether graft survival could be improved by the additional use of the angiogenic cytokine erythropoietin (EPO). Thirty-five Lewis rats underwent coronary artery ligation and, two weeks later, were randomized to receive in-scar injections of control medium, skeletal myoblasts (5x10(6)) or skeletal myoblasts with EPO started the day before transplantation and continued for two weeks (500 U/kg three times a week). A fourth group was treated by EPO alone without injections. Function was assessed by 2D echocardiography before transplantation and one month thereafter. Compared with controls and hearts treated by EPO-alone, those transplanted with myoblasts yielded a significantly better recovery of LV ejection fraction, irrespective of whether they had received EPO or not. Neither the area of myoblast engraftment, nor angiogenesis differed between the myoblast-alone and the myoblast+EPO groups. Apoptosis was hardly detectable and, therefore, unaffected by EPO therapy. In this model, EPO failed to improve myoblast engraftment and postinfarction LV function. These negative findings justify to pursue the search for alternate cell survival-enhancing strategies.
INSERM U 633, Laboratoire d'Etude des Greffes et Prothèses Cardiaques, Hôpital Broussais; Assistance Publique-Hôpitaux de Paris, Ecole de Chirurgie, Paris, France.
Sylvain
S
Chanséaume
Kasra
K
Azarnoush
Agnès
A
Maurel
Valérie
V
Bellamy
Séverine
S
Peyrard
Patrick
P
Bruneval
Albert A
AA
Hagège
Philippe
P
Menasché
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival; D017690:Cell Transplantation; D002478:Cells, Cultured; D004452:Echocardiography; D004921:Erythropoietin / Q000494:pharmacology*; D006400:Hematocrit; D020287:In Situ Nick-End Labeling; D032446:Myoblasts / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D016277:Ventricular Function, Left
D004921:Erythropoietin