Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration
Susan M. Majka, Kathyjo A. Jackson, Kirsten A. Kienstra, Mark W. Majesky, Margaret A. Goodell, Karen K. Hirschi
Susan M. Majka, Kathyjo A. Jackson, Kirsten A. Kienstra, Mark W. Majesky, Margaret A. Goodell, Karen K. Hirschi
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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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Figure 5

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Skeletal muscle-derived SP cells engraft into vascular endothelium. Six-...
Skeletal muscle-derived SP cells engraft into vascular endothelium. Six- to eight-week-old C57Bl/6 mice were anesthetized with Avertin, and both TA muscles were injected with 25 μl of a 1 mg/ml cardiotoxin. After 8 or 24 hours, the right limb TA muscle was injected with 2,000 LacZ-positive muscle SP cells, and the left leg was injected with HBSS alone. After 4 weeks, the TA muscles of each of four experimental animals were harvested and processed for frozen sectioning and immunohistochemical analysis. All sections were immunostained for β-gal and costained for either ICAM-2 or desmin to detect injury-induced engraftment of LacZ-positive SP cells into regenerated vascular endothelium and smooth muscle, respectively. β-gal expression in vascular structures was colocalized only with ICAM-2: (a and b) bright field, boxes indicate costained vessels; (c and d) β-gal immunohistochemistry; (e and f) ICAM-2 immunohistochemistry; (g and h) β-gal and ICAM-2 fluorescent images were merged to reveal areas of costaining, as evidenced by the yellow staining pattern. Magnification, ×400 (a, c, e, g); ×1,000 (b, d, f, h, and inset boxes in c, e, and g).