&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