Submitted to: Journal of Clinical Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/1/2002
Publication Date: 1/1/2003
Citation: Majka, S.M., Jackson, K.A., Kienstra, K.A., Majesky, M.W., Goodell, M.A., Hirschi, K.K. 2003. Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. The Journal of Clinical Investigation. 111(1):71-79. Interpretive Summary: Stem cells have been identified within adult muscle tissue, and contribute to the blood vessel repair under muscle injury. We examined the stem cells in genetically specific mice populations. Muscle stem cells were injected into injured muscle of genetically compatible mice. Distinct populations of vascular progenitors are derived from bone marrow, reside in skeletal muscle and have different roles during injury-related vascular regeneration. These results provide insight into adult blood vessel regeneration.
Technical 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.