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Transplanted hematopoietic stem cells demonstrate impaired sarcoglycan expression after engraftment into cardiac and skeletal muscle
Karen A. Lapidos, … , Averil Ma, Elizabeth M. McNally
Karen A. Lapidos, … , Averil Ma, Elizabeth M. McNally
Published December 1, 2004
Citation Information: J Clin Invest. 2004;114(11):1577-1585. https://doi.org/10.1172/JCI23071.
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Article

Transplanted hematopoietic stem cells demonstrate impaired sarcoglycan expression after engraftment into cardiac and skeletal muscle

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Abstract

Pluripotent bone marrow–derived side population (BM-SP) stem cells have been shown to repopulate the hematopoietic system and to contribute to skeletal and cardiac muscle regeneration after transplantation. We tested BM-SP cells for their ability to regenerate heart and skeletal muscle using a model of cardiomyopathy and muscular dystrophy that lacks δ-sarcoglycan. The absence of δ-sarcoglycan produces microinfarcts in heart and skeletal muscle that should recruit regenerative stem cells. Additionally, sarcoglycan expression after transplantation should mark successful stem cell maturation into cardiac and skeletal muscle lineages. BM-SP cells from normal male mice were transplanted into female δ-sarcoglycan–null mice. We detected engraftment of donor-derived stem cells into skeletal muscle, with the majority of donor-derived cells incorporated within myofibers. In the heart, donor-derived nuclei were detected inside cardiomyocytes. Skeletal muscle myofibers containing donor-derived nuclei generally failed to express sarcoglycan, with only 2 sarcoglycan-positive fibers detected in the quadriceps muscle from all 14 mice analyzed. Moreover, all cardiomyocytes with donor-derived nuclei were sarcoglycan-negative. The absence of sarcoglycan expression in cardiomyocytes and skeletal myofibers after transplantation indicates impaired differentiation and/or maturation of bone marrow–derived stem cells. The inability of BM-SP cells to express this protein severely limits their utility for cardiac and skeletal muscle regeneration.

Authors

Karen A. Lapidos, Yiyin E. Chen, Judy U. Earley, Ahlke Heydemann, Jill M. Huber, Marcia Chien, Averil Ma, Elizabeth M. McNally

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Figure 3

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BM-SP cells engraft into skeletal muscle but have limited sarcoglycan ex...
BM-SP cells engraft into skeletal muscle but have limited sarcoglycan expression. Normal male quadriceps (A_C) and female Sgcd–/– recipient quadriceps muscle sections (D_F) were stained for γ-sarcoglycan immunoreactivity (A and D, red) and then subjected to FISH with a Y chromosome_specific probe, Y-1 (B and E, green). The merged images along with DAPI staining (blue) in C and F show nuclear localization of the Y-1 signals. Arrows in D_F indicate Y-1_positive cells engrafted between myofibers. The arrowheads in D_F show a Y-1_positive nucleus inside a myofiber. Despite engraftment, sarcoglycan expression was not restored. (G) A single γ-sarcoglycan_positive cell detected in δ-sarcoglycan_null quadriceps after transplantation with BM-SP cells. (H) A serial section of the same donor-derived cell also expresses δ-sarcoglycan. (I) Immunostaining of a transplant-recipient muscle with dystrophin and concomitant FISH with the Y-1 probe to detect donor nuclei (dystrophin, red; Y-1, green; DAPI, blue). Arrowheads in I indicate 3 Y chromosome signals in the central or peripheral nucleus position. Scale bars: 50 μm.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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