Function of skeletal muscle tissue formed after myoblast transplantation into irradiated mouse muscles.
1. Pretreatment of muscles with ionising radiation enhances tissue formation by transplanted myoblasts but little is known about the effects on muscle function. We implanted myoblasts from an expanded, male-donor-derived, culture (i28) into X-ray irradiated (16 Gy) or irradiated and damaged soleus muscles of female syngeneic mice (Balb/c). Three to 6 months later the isometric 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 of 106 myoblasts abolished these deficiencies and innervation appeared normal. 3. Cryodamage of irradiated solei produced muscle remnants with few (1-50) or no fibres. Additional myoblast implantation led to formation of large muscles (25 % above normal) containing numerous small-diameter fibres. Upon direct electrical stimulation, these muscles produced considerable twitch (53 % of normal) and tetanic forces (35 % of normal) but innervation was insufficient as indicated by weak nerve-evoked contractions and elevated ACh sensitivity. 4. In control experiments on irradiated muscles, reinnervation was found to be less complete after botulinum toxin paralysis than after nerve crush indicating that proliferative arrest of irradiated Schwann cells may account for the observed innervation deficits. 5. Irradiation appears to be an effective pretreatment for improving myoblast transplantation. The injected cells can even produce organised contractile tissue replacing whole muscle. However, impaired nerve regeneration limits the functional performance of the new muscle.
Wernig
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Department of Physiology, Neurophysiology, University of Bonn, Wilhelmstrasse 31, D-53111 Bonn, Germany. wernig@physio.uni-bonn.de
Zweyer
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M
Irintchev
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D000818:Animals; D001369:Axons / Q000502:physiology / Q000528:radiation effects; D001905:Botulinum Toxins / Q000633:toxicity; D002455:Cell Division / Q000528:radiation effects; D017690:Cell Transplantation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D007537:Isometric Contraction / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D018482:Muscle, Skeletal / Q000502:physiology* / Q000528:radiation effects*; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology / Q000528:radiation effects; D010243:Paralysis / Q000139:chemically induced; D012583:Schwann Cells / Q000528:radiation effects / Q000637:transplantation; D014965:X-Rays
D001905:Botulinum Toxins