Selection of multipotent cells and enhanced muscle reconstruction by myogenic macrophage-secreted factors.
Skeletal muscle regeneration relies on satellite cells, a population of myogenic precursors. Inflammation also plays a determinant role in the process, as upon injury, macrophages are attracted by the damaged myofibers and the activated satellite cells and act as key elements of dynamic muscle supportive stroma. Yet, it is not known how macrophages interact with the more profound stem cells of the satellite cell niche. Here we show that in the presence of a murine macrophage conditioned medium (mMCM) a subpopulation of multipotent cells could be selected and expanded from adult rat muscle. These cells were small, round, poorly adhesive, slow-growing and showed mesenchymal differentiation plasticity. At the same time, mMCM showed clear myogenic capabilities, as experiments with satellite cells mechanically isolated from suspensions of single myofibers showed that the macrophagic factors inhibited their tendency to shift towards adipogenesis. In vivo, intramuscular administrations of concentrated mMCM in a rat model of extensive surgical ablation dramatically improved muscle regeneration. Altogether, these findings suggest that macrophagic factors could be of great help in developing therapeutic protocols with myogenic stem cells.
Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy.
Alberto
A
Malerba
Libero
L
Vitiello
Daniela
D
Segat
Emanuela
E
Dazzo
Marco
M
Frigo
Ilaria
I
Scambi
Paolo
P
De Coppi
Luisa
L
Boldrin
Laura
L
Martelli
Alessandra
A
Pasut
Chiara
C
Romualdi
Rosa Grazia
RG
Bellomo
Jacopo
J
Vecchiet
Maurizio David
MD
Baroni
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000737:chemistry*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology*; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000502:physiology*
D017077:Culture Media, Conditioned