Can cold or heat shock improve skeletal myoblast engraftment in infarcted myocardium?
OBJECTIVE
Cell death remains a major limitation of skeletal myoblast (SM) transplantation but the patterns of cell survival and proliferation in heart and their potential modulation by thermic stresses like heat shock (HS) and cryopreservation (Cryo) are still incompletely characterized.


METHODS
To track SMs in situ, we developed a dual-marker system based on the semiconservative expression of the foreign soluble protein, beta-Galactosidase (beta-Gal) and the constitutive expression of the Y chromosome in a myocardial infarction model. Control medium or Lewis male rat SMs (fresh or subjected to Cryo or HS) were injected in Lewis female rats.


RESULTS
There was a massive cell loss early after transplantation in the fresh group, which was only partially compensated for by a subsequent proliferation. Conversely, both Cryo and HS significantly improved early cell survival but blunted subsequent proliferation so that, at 15 days posttransplantation, the total number of engrafted donor-derived Y-positive cells did not differ significantly between the three groups. Most of them expressed a skeletal muscle phenotype.


CONCLUSIONS
These data confirm the high death rate of in-scar transplanted myoblasts, demonstrate the ability of those that survive to proliferate and differentiate along the myogenic pathway but do not support the efficacy of either Cryo or HS for increasing the ultimate magnitude of myoblast engraftment.
Maurel
Agnès
A
1 INSERM U633, Laboratoire d'Etude des Greffes et Prothèses Cardiaques, Hôpital Broussais, Paris, France.
Azarnoush
Kasra
K
Sabbah
Laurent
L
Vignier
Nicolas
N
Le Lorc'h
Marc
M
Mandet
Chantal
C
Bissery
Alvine
A
Garcin
Isabelle
I
Carrion
Claire
C
Fiszman
Marc
M
Bruneval
Patrick
P
Hagege
Alain
A
Carpentier
Alain
A
Vilquin
Jean-Thomas
JT
Menasché
Philippe
P
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D003080:Cold Temperature; D015925:Cryopreservation; D005260:Female; D005819:Genetic Markers; D006085:Graft Survival; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response; D006358:Hot Temperature; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy*; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D014998:Y Chromosome; D001616:beta-Galactosidase / Q000235:genetics
D005819:Genetic Markers; D018840:HSP70 Heat-Shock Proteins; D001616:beta-Galactosidase