Transplantation of normal and DMD myoblasts expressing the telomerase gene in SCID mice.
The limited proliferative capacity of dystrophic human myoblasts severely limits their ability to be genetically modified and used for myoblast transplantation. The forced expression of the catalytic subunit of telomerase can prevent telomere erosion and can immortalize different cell types. We thus tested the ability of telomerase to immortalize myoblasts and analyzed the effect of telomerase expression on the success of myoblast transplantation. Telomerase expression did not significantly extend the human myoblast life span. The telomerase expressing myoblasts were nonetheless competent to participate in myofiber formation after infection with the retroviral vector. Although the new fibers obtained are less numerous than after the transplantation of normal myoblasts, these results demonstrate that the forced expression of telomerase does not block the ability of normal or dystrophic myoblasts to differentiate in vivo. It will be now necessary to determine the factors that prevent telomerase from extending the life span of human myoblasts before the potential of this intervention can be fully examined.
Seigneurin-Venin
S
S
Laboratoire de Génétique Humaine, Université Laval and CHUQ Pavillon CHUL, Québec, Canada.
Bernard
V
V
Moisset
P A
PA
Ouellette
M M
MM
Mouly
V
V
Di Donna
S
S
Wright
W E
WE
Tremblay
J P
JP
D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D002455:Cell Division; D017690:Cell Transplantation; D016922:Cellular Senescence; D002648:Child; D003893:Desmin / Q000032:analysis; D016189:Dystrophin / Q000032:analysis; D018014:Gene Transfer Techniques; D006085:Graft Survival; D006801:Humans; D007223:Infant; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009132:Muscles / Q000166:cytology* / Q000201:enzymology* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D013049:Spectrin / Q000032:analysis; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D003893:Desmin; D016189:Dystrophin; D013049:Spectrin; D019098:Telomerase