L. Heslop et al., Transplanted primary neonatal myoblasts can give rise to functional satellite cells as identified using the Myf5(nlacZ/+) mouse, GENE THER, 8(10), 2001, pp. 778-783
Myoblast transplantation is a potential therapeutic approach for the geneti
c modification of host skeletal muscle tissue. To be considered an effectiv
e, long-lived method of delivery, however, it is essential that at least a
proportion of the transplanted cells also retain their proliferative potent
ial. We sought to investigate whether transplanted neonatal myoblasts can c
ontribute to the satellite cell compartment of adult skeletal muscle by usi
ng the Myf5(nlacZ/+) mouse. The Myf5(nlacZ/+) mouse has nlacZ targeted to t
he Myf5 locus resulting in beta -galactosidase activity in quiescent satell
ite cells. Following transplantation, beta -galactosidase-labelled nuclei w
ere detected in host muscles, showing that donor cells had been incorporate
d. Significantly, beta -galactosidase-positive, and therefore donor-derived
, satellite cells were detected When placed in culture, beta -galactosidase
marked myogenic cells emanated from the parent fibre. These observations d
emonstrate that cell transplantation not only results in the incorporation
of donor nuclei into the host muscle syncytia, but also that the donor cell
s can become functional satellite cells. The Myf5(nlacZ/+) mouse therefore
provides a novel and specific marker for determining the contribution of tr
ansplanted cells to the satellite cell pool.