Transplantation of normal and DMD myoblasts expressing the telomerase genein SCID mice

The limited proliferative capacity of dystrophic human myoblasts severely l imits their ability to be genetically modified and used for myoblast transp lantation. 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 lif e span. The telomerase expressing myoblasts were nonetheless competent to p articipate in myofiber formation after infection with the retroviral vector . Although the new fibers obtained are less numerous than after the transpl antation of normal myoblasts, these results demonstrate that the forced exp ression of telomerase does not block the ability of normal or dystrophic my oblasts to differentiate in vivo. It will be now necessary to determine the factors that prevent telomerase from extending the life span of human myob lasts before the potential of this intervention can be fully examined. (C) 2000 Academic Press.