FUNCTIONAL IMPROVEMENT OF DAMAGED ADULT-MOUSE MUSCLE BY IMPLANTATION OF PRIMARY MYOBLASTS

1. Myoblasts from expanded primary cultures were implanted into cryoda maged soleus muscles of adult BALB/c mice. One to four months later is ometric tension recordings were performed in vitro, and the male donor cells implanted into female hosts were traced on histological section s using a Y-chromosome-specific probe. The muscles were either mildly or severely cryodamaged, which led to reductions in tetanic muscle for ce to 33 % (n = 9 muscles, 9 animals) and 70 % (n = 11) of normal, res pectively. Reduced forces resulted from deficits in regeneration of mu scle tissue as judged from the reduced desmin-positive cross-sectional areas (34 and 66 % of control, respectively). 2. Implantation of 10(6 ) myogenic cells into severely cryodamaged muscles more than doubled m uscle tetanic force (to 70 % of normal, n = 14), as well as specific f orce (to 66 % of normal). Absolute and relative amounts of desmin-posi tive muscle cross-sectional areas were significantly increased indicat ing improved microarchitecture and less fibrosis. Newly formed muscle tissue was fully innervated since the tetanic forces resulting from di rect and indirect (nerve-evoked) stimulation were equal. Endplates wer e found on numerous Y-positive muscle fibres. 3. As judged from their position under basal laminae of muscle fibres and the expression of M- cadherin, donor-derived cells contributed to the pool of satellite cel ls on small- and large-diameter muscle fibres. 4. Myoblast implantatio n after mild cryodamage and in undamaged muscles had little or no func tional or structural effects; in both preparations only a few Y-positi ve muscle nuclei were detected. It is concluded that myoblasts from ex panded primary cultures - unlike permanent cell lines - significantly contribute to muscle regeneration only when previous muscle damage is extensive and loss of host satellite cells is severe.