FUNCTION OF SKELETAL MUSCLE TISSUE FORMED AFTER
MYOBLAST TRANSPLANTATION
INTO IRRADIATED MOUSE
MUSCLES
A.
Wernig, M. Zweyer, A. Irintchev
Pretreatment of
host muscles with ionising radiation enhances the formation of donor-derived
tissue after myoblast transplantation in the mouse
but there is little evidence for improvement of muscle function. To investigate
this, we implanted myoblasts from an expanded,
male-donor derived, primary culture (i28) into X-ray
irradiated (16 Gy) or irradiated and damaged soleus muscles of female syngenic
mice (Balb/c). Three to 6 months later the isometric
contractile properties of transplanted and control muscles were studied in vitro, and the Y chromosome positive
progeny of the implanted cells was visualised on muscle cross-sections.
Irradiated and vehicle-injected muscles had significantly smaller
weights than untreated solei and produced less twitch
and tetanic tension (all about 18%). Such deficits
were not found in irradiated solei implanted with 106
myoblasts. Increase of muscle mass and strength was
due to the integration of donor-derived cells. No deficits in nerve-evoked
tension were found.
Repeated freezing/thawing in situ of irradiated muscles led to formation of soleus remnants devoid of or containing only small amounts of contractile tissue (1-50
muscle fibres). Myoblasts (106) implanted
into such destructed muscles generated numerous muscle fibres (1200-5000 per
muscle). Upon direct electrical stimulation these fibres produced considerable
twitch (53% of normal) and tetanic tensions (35%).
The newly-formed muscles were, however, insufficiently innervated presumably due to radiation
mediated arrest of Schwann cells. Separate studies on
nerve regeneration following x-irradiation and nerve crush or botulinum application will be demonstrated. In any case,
even after complete muscle destruction the disorganised suspension of donor
cells will produce new organised contractile tissue thus replacing the host
muscle. Limiting factor is the reduced capacity of the nerve to regenerate
after x-irradiation.
Apart from these results, the role of the satellite cell in muslce fiber repair as well as a
possible source for pluripotent stem cells will be
discussed. The deviating behaviour of human myogenic
cells in their limited proliferative capacity and telomere lenght related
senescence will be mentioned.
Department of Physiology,