Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration
Susan M. Majka, … , Margaret A. Goodell, Karen K. Hirschi
Susan M. Majka, … , Margaret A. Goodell, Karen K. Hirschi
Published January 1, 2003
Citation Information: J Clin Invest. 2003;111(1):71-79. https://doi.org/10.1172/JCI16157.
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Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration

Abstract

Vascular progenitors were previously isolated from blood and bone marrow; herein, we define the presence, phenotype, potential, and origin of vascular progenitors resident within adult skeletal muscle. Two distinct populations of cells were simultaneously isolated from hindlimb muscle: the side population (SP) of highly purified hematopoietic stem cells and non-SP cells, which do not reconstitute blood. Muscle SP cells were found to be derived from, and replenished by, bone marrow SP cells; however, within the muscle environment, they were phenotypically distinct from marrow SP cells. Non-SP cells were also derived from marrow stem cells and contained progenitors with a mesenchymal phenotype. Muscle SP and non-SP cells were isolated from Rosa26 mice and directly injected into injured muscle of genetically matched recipients. SP cells engrafted into endothelium during vascular regeneration, and non-SP cells engrafted into smooth muscle. Thus, distinct populations of vascular progenitors are resident within skeletal muscle, are derived from bone marrow, and exhibit different cell fates during injury-induced vascular regeneration.

Authors

Susan M. Majka, Kathyjo A. Jackson, Kirsten A. Kienstra, Mark W. Majesky, Margaret A. Goodell, Karen K. Hirschi

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Vascular progenitors within skeletal muscle are derived from bone marrow...
Vascular progenitors within skeletal muscle are derived from bone marrow. SP cells were isolated from bone marrow of Rosa26 mice and stably engrafted into lethally irradiated, genetically matched recipients. After 5 or 12 months, the hindlimb musculature was excised and examined for the presence of LacZ-positive vascular progenitors. Percoll-fractionated muscle cells were stained with Hoechst dye and loaded with FDG, then subjected to FACS to isolate muscle SP and non-SP populations and determine whether they exhibit β-gal activity. (a) The mean ± SD of LacZ-positive SP and non-SP cells among three mice at 5 months after transplant was 39.0% ± 16.4% and 10.6% ± 1.9%, respectively. (b) At 12 months after transplantation, the mean ± SD of LacZ-positive SP and non-SP cells among three mice was 89.4% ± 8.2% and 87.5% ± 5.2%, respectively.