Function of skeletal muscle tissue formed after myoblast transplantation into irradiated mouse muscles

1. Pretreatment of muscles with ionising radiation enhances tissue formatio n by transplanted myoblasts but little is known about the effects on muscle function. We implanted myoblasts from an expanded, male-donor-derived, cul ture (i28) into X-ray irradiated (16 Gy) or irradiated and damaged soleus m uscles of female syngeneic mice (Balb/c). Three to 6 months later the isome tric contractile properties of the muscles were studied in vitro, and donor nuclei were visualised in muscle sections with a Y chromosome-specific DNA probe. 2. Irradiated sham-injected muscles had smaller masses than untreated solei and produced less twitch and tetanic force (all by about 18%). Injection o f 10(6) myoblasts abolished these deficiencies and innervation appeared nor mal. 3. Cryodamage of irradiated solei produced muscle remnants with few (1-50) or no fibres. Additional myoblast implantation led to formation of large mu scles (25% above normal) containing numerous small-diameter fibres. Upon di rect electrical stimulation, these muscles produced considerable twitch (53 % of normal) and tetanic forces (35% of normal) but innervation was insuffi cient as indicated by weak nerve-evoked contractions and elevated ACh sensi tivity. 4. In control experiments on irradiated muscles, reinnervation was found to be less complete after botulinum toxin paralysis than after nerve crush in dicating that proliferative arrest of irradiated Schwann cells may account fbr the observed innervation deficits. 5. Irradiation appears to be an effective pretreatment for improving myobla st transplantation. The injected cells can even produce organised contracti le tissue replacing whole muscle. However, impaired nerve regeneration limi ts the functional performance of the new muscle.