TRANSFORMING GROWTH-FACTOR-BETA-1 FACILITATES ESTABLISHING CLONAL POPULATIONS OF OVINE MUSCLE SATELLITE CELLS

Myogenic cells isolated from lamb fetuses (approximately mid-gestation ) exhibited a concentration-dependent decrease in myogenic cell prolif eration in response to transforming growth factor (TGF) beta-1 (P <.00 1). Half-maximal inhibition of proliferation occurred at approximately .05 ng of TGF beta-1/mL and maximal inhibition of proliferation occur red at approximately .1 ng of TGF beta-1/mL. The specificity of this i nhibition was confirmed by neutralization of the activity following ex posure to a TGF beta antibody. The TGF beta-1 also suppressed prolifer ation of ovine satellite cells isolated from 5-d-old lambs (P <.0035), but to a lesser extent than observed for embryonic cells. In contrast , TGF beta-1 did not significantly suppress serum-stimulated prolifera tion of ovine satellite cells isolated from 30- or 150-d-old lambs. Si milarly, TGF beta-1 did not suppress proliferation of skeletal muscle fibroblastlike cells isolated from either fetal lambs or 150-d-old lam bs. In fact, proliferation of fibroblast-like cells derived from embry onic ovine muscle was enhanced by exposure to TGF beta-1 at all levels tested; however, a concentration-dependent response was not observed. Media transfer experiments showed that conditioning of culture media by postnatally derived cells did not render TGF beta-1 inactive. The s tudies described in this manuscript suggest that sensitivity of ovine myogenic cells to the antiproliferative effect of TGF-beta may vary wi th the stage of development. Additionally, the ability of TGF beta to suppress fusion of ovine satellite cells from 30- or 150-d-old lambs, while having no effect on their proliferation, makes this growth facto r very useful in establishing clonal populations of these cells.