&p.1:Abstract It is commonly accepted, that regenerative ca-
pacity of striated muscle is confined to skeletal muscle
by activation of satellite cells that normally reside quies-
cent between the plasmalemma and the basement mem-
brane of muscle fibers. Muscular dystrophies are charac-
terized by repetitive cycles of de- and regeneration of
skeletal muscle fibers and by the frequent involvement of
the cardiac muscle. Since during the longstanding course
of muscular dystrophies there is a permanent demand of
myogenic progenitors we hypothesized that this may ne-
cessitate a recruitment of additional myogenic precursors
from an undifferentiated, permanently renewed cell pool,
such as bone marrow (BM) cells. To this end normal and
dystrophic (mdx) female mice received bone marrow
transplantation (BMT) from normal congenic male donor
mice. After 70 days, histological sections of skeletal and
cardiac muscle from BMT mice were probed for the do-
nor-derived Y chromosomes. In normal BMT recipients,
no Y chromosome-containing myonuclei were detected,
either in skeletal or in cardiac muscle. However, in all
samples from dystrophic mdx skeletal muscles Y chro-
mosome-specific signals were detected within muscle fi-
ber nuclei, which additionally were found to express the
myoregulatory proteins myogenin and myf-5. Moreover,
in the hearts of BMT-mdx mice single cardiomyocytes
with donor derived nuclei were identified, indicating,
that even cardiac muscle cells are able to regenerate by
recruitment of circulating BM-derived progenitors. Our
findings suggest that further characterization and identi-
fication of the BM cells capable of undergoing myogenic
differentiation may have an outstanding impact on thera-
peutic strategies for diseases of skeletal and cardiac mus-
cle.
&kwd:Key words Dystrophin deficient · mdx mouse ·
Duchenne muscular dystrophy · Satellite cells ·
Muscle regeneration · Cardiac muscle · Bone marrow
transplantation&bdy:
Introduction
After embryonic development, myonuclei in both types
of striated muscle, i.e., skeletal and cardiac muscle, be-
come mitotically inactive. In contrast to cardiac muscle,
which is thought not to be capable of regeneration, re-
generative capacity is conferred on skeletal muscle by
satellite cells (Mauro 1961). These mononucleated cells
represent a pool of myogenic precursors that reside qui-
escently between the plasma membrane and basal lamina
of the muscle fibers. Upon several stimuli, e.g., degener-
ation of the “host fiber” they become mitotically active
beneath the remaining basement membrane scaffold and
by cell-fusion mature muscle fibers can be regenerated
(Benoit and Belt 1970; Carlson and Faulkner 1983;
Bischoff and Heintz 1994).
Repetitive cycles of muscle degeneration and subse-
quent regeneration take place in muscular dystrophies, a
group of inherited disorders characterized by progressive
muscular weakness and wasting (Dubowitz 1985). Con-
cerning the huge and permanent demand of satellite cells
during the course of muscular dystrophies (Laguens
R.E. Bittner (
✉
) · S. Ivanova · B. Streubel
Institute of Anatomy, Department 3, University of Vienna,
Währingerstrasse 13, A-1090 Vienna, Austria
e-mail: reginald.bittner@univie.ac.at,
Tel.: +43-1-4277-61182, Fax: +43-1-4277-61198
C. Schöfer · K. Weipoltshammer · F. Wachtler
Institute of Histology and Embryology, University of Vienna,
Schwarzspanierstrasse 17, A-1090 Vienna, Austria
E. Hauser · M. Freilinger
Clinic of Pediatrics, Vienna Medical School, University of Vienna,
Währinger Gürtel 18–20, A-1090 Vienna, Austria
H. Höger
Research Institute for Laboratory Animal Breeding,
University of Vienna, Brauhausgasse 34,
A-2325 Himberg, Austria
A. Elbe-Bürger
Department of Dermatology,
Division of Immunology, Allergy and Infectious Diseases,
University of Vienna Medical School,
Vienna International Research Cooperation Center,
Brunner Str. 59, A-1235 Vienna, Austria&/fn-block:
Anat Embryol (1999) 199:391–396 © Springer-Verlag 1999
ORIGINAL ARTICLE
&roles:Reginald E. Bittner · Christian Schöfer
Klara Weipoltshammer · Silva Ivanova
Berthold Streubel · Erwin Hauser
Michael Freilinger · Harald Höger
Adelheid Elbe-Bürger · Franz Wachtler
Recruitment of bone-marrow-derived cells by skeletal
and cardiac muscle in adult dystrophic mdx mice
&misc:Accepted: 27 October 1998