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The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers are silent despite long-term engraftment PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Wernig, G., Janzen, V., SCHAFER, R., Zweyer, M., Knauf, U., Hoegemeier, O., Mundegar, R. R., Garbe, S., Stier, S., Franz, T., Wernig, M., Wernig, A. 2005; 102 (33): 11852-11857

Abstract

Bone-marrow-derived cells can contribute nuclei to skeletal muscle fibers. However, serial sectioning of muscle in mdx mice implanted with GFP-labeled bone marrow reveals that only 20% of the donor nuclei chronically incorporated in muscle fibers show dystrophin (or GFP) expression, which is still higher than the expected frequency of "revertant" fibers, but there is no overall increase above controls over time. Obviously, the vast majority of incorporated nuclei either never or only temporarily turn on myogenic genes; also, incorporated nuclei eventually loose the activation of the beta-actin::GFP transgene. Consequently, we attempted to enhance the expression of dystrophin. In vivo application of the chromatin-modifying agents 5-azadeoxycytidine and phenylbutyrate as well as local damage by cardiotoxin injections caused a small increase in dystrophin-positive fibers without abolishing the appearance of "silent" nuclei. The results thus confirm that endogenous repair processes and epigenetic modifications on a small-scale lead to dystrophin expression from donor nuclei. Both effects, however, remain below functionally significant levels.

View details for DOI 10.1073/pnas.0502507102

View details for Web of Science ID 000231317000051

View details for PubMedID 16085712

View details for PubMedCentralID PMC1187970