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Functional improvement of damaged adult mouse muscle by implantation of primary myoblasts.

1. Myoblasts from expanded primary cultures were implanted into cryodamaged soleus muscles of adult BALB/c mice. One to four months later isometric tension recordings were performed in vitro, and the male donor cells implanted into female hosts were traced on histological sections using a Y‐chromosome‐specific probe. The muscles were either mildly or severely cryodamaged, which led to reductions in tetanic muscle force to 33% (n = 9 muscles, 9 animals) and 70% (n = 11) of normal, respectively. Reduced forces resulted from deficits in regeneration of muscle 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 muscle tetanic force (to 70% of normal, n = 14), as well as specific force (to 66% of normal). Absolute and relative amount of desmin‐positive muscle cross‐sectional areas were significantly increased indicating improved microarchitecture and less fibrosis. Newly formed muscle tissue was fully innervated since the tetanic forces resulting from direct and indirect (nerve‐evoked) stimulation were equal. Endplates were 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 cells on small‐ and large‐diameter muscle fibres. 4. Myoblast implantation after mild cryodamage and in undamaged muscles had little or no functional or structural effects; in both preparations only a few Y‐positive muscle nuclei were detected. It is concluded that myoblasts from expanded 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.