Autologous myoblast transplantation for chronic ischemic mitral regurgitation.
OBJECTIVE
This study was designed to assess whether post-myocardial infarction (MI) in-scar transplantation of skeletal myoblasts (SM) could reduce chronic ischemic mitral regurgitation (MR) by decreasing left ventricular (LV) remodeling.


BACKGROUND
Extensive work has confirmed the relationship between ischemic MR and post-myocardial infarction (MI) remodeling of the LV.


METHODS
An infero-posterior MI was created in 13 sheep, thereby resulting in increasing MR. Two months post-MI, the animals were randomized and in-scar injected with expanded autologous SM (n = 6, mean: 251 x 10(6) cells) or culture medium only (n = 7). Three-dimensional echocardiography was performed at baseline, before transplantation, and for two months thereafter (sacrifice), with measurements of LV end-diastolic and end-systolic volumes (ESV), ejection fraction (EF), MR stroke volume, and leaflet tethering distance; wall motion score index (WMSi) was assessed by two-dimensional echo.


RESULTS
Measurements were similar between groups at baseline and before transplantation. At sacrifice, transplantation was found to have reduced MR progression (regurgitant volume change: -1.83 +/- 0.32 ml vs. 5.9 +/- 0.7 ml in control group, p < 0.0001) and tethering distance (-0.41 +/- 0.09 cm vs. 0.44 +/- 0.12 cm in control group, p < 0.001), with significant improvement of EF (2.01 +/- 0.94% vs. -4.86 +/- 2.23%, p = 0.02), WMSi (-0.25 +/- 0.11 vs. 0.13 +/- 0.03 in controls, p < 0.01) and a trend to a lesser increase in ESV (23.3 +/- 3.5 ml vs. 35.4 +/- 4.2 ml in control group, p = 0.055).


CONCLUSIONS
Autologous skeletal myoblast transplantation attenuates mild-to-moderate chronic ischemic MR, which otherwise is progressive, by decreasing tethering distance and improving EF and wall motion score, thereby enhancing valve coaptation. These data shed additional light on the mechanism by which skeletal myoblast transplantation may be cardioprotective.
Messas
Emmanuel
E
Université René Descartes Paris 5, Faculté de Médecine René Descartes Paris 5, Paris, France. emmanuel.messas@nck.aphp.fr
Bel
Alain
A
Morichetti
Miguel Cortes
MC
Carrion
Claire
C
Handschumacher
Marc D
MD
Peyrard
Séverine
S
Vilquin
Jean Thomas
JT
Desnos
Michel
M
Bruneval
Patrice
P
Carpentier
Alain
A
Menasché
Philippe
P
Levine
Robert A
RA
Hagège
Albert A
AA
D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D002908:Chronic Disease; D002921:Cicatrix; D004195:Disease Models, Animal; D004452:Echocardiography; D015552:Injections, Intralesional; D008944:Mitral Valve Insufficiency / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy*; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications*; D012756:Sheep; D013318:Stroke Volume; D014182:Transplantation, Autologous; D020257:Ventricular Remodeling / Q000502:physiology