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.
Irintchev
A
A
Department of Physiology, University of Bonn, Germany.
Langer
M
M
Zweyer
M
M
Theisen
R
R
Wernig
A
A
D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D002452:Cell Count; D002454:Cell Differentiation; D017690:Cell Transplantation / Q000502:physiology*; D002478:Cells, Cultured; D003893:Desmin / Q000378:metabolism; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D005615:Freezing; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000293:injuries / Q000502:physiology*; D012038:Regeneration / Q000502:physiology
D015820:Cadherins; D003893:Desmin; C070896:M-cadherin