Muscle Satellite Cells and Endothelial Cells: Close Neighbors and Privileged Partners

Abstract

Genetically engineered mice (Myf5 nLacZ/؉ , Myf5GFP-P/؉ ) allowing direct muscle satellite cell (SC) visualization indicate that, in addition to being located beneath myofiber basal laminae, SCs are strikingly close to capillaries. After GFP ؉ bone marrow transplantation, blood-borne cells occupying SC niches previously depleted by irradiation were similarly detected near vessels, thereby corroborating the anatomical stability of juxtavascular SC niches. Bromodeoxyuridine pulse-chase experiments also localize quiescent and less quiescent SCs near vessels. SCs, and to a lesser extent myonuclei, were nonrandomly associated with capillaries in humans. Significantly, they were correlated with capillarization of myofibers, regardless to their type, in normal muscle. They also varied in paradigmatic physiological and pathological situations associated with variations of capillary density, including amyopathic dermatomyositis, a unique condition in which muscle capillary loss occurs without myofiber damage, and in athletes in whom capillaries increase in number. Endothelial cell (EC) cultures specifically enhanced SC growth, through IGF-1, HGF, bFGF, PDGF-BB, and VEGF, and, accordingly, cycling SCs remained mainly juxtavascular. Conversely, differentiating myogenic cells were both proangiogenic in vitro and spatiotemporally associated with neoangiogenesis in muscular dystrophy. Thus, SCs are largely juxtavascular and reciprocally interact with ECs during differentiation to support angio-myogenesis. INTRODUCTIONMuscle tissue repair is a complex biological process that crucially involves activation of stem cells. Skeletal muscle contains two different stem cell types: 1) myogenic stem cells, so-called satellite cells (SCs), that reside beneath the basal lamina of muscle fibers (Mauro, 1961) and express both NCAM/CD56 and early myogenic cell markers such as M-cadherin, Pax7, and Myf5 (Beauchamp et al., 2000;Seale et al., 2000;Hawke and Garry, 2001; Bischoff and FranziniArmstrong, 2004) and 2) interstitial multipotent stem cells, which are extralaminal, exhibit fibroblastic morphology and do not express myogenic markers (Asakura et al., 2001;Tamaki et al., 2002). SCs are primarily quiescent in skeletal muscle, can self-renew (Collins et al., 2005) and upon activation, proliferate and further differentiate to become fusioncompetent myoblasts and ensure muscle regeneration (Hawke and Garry, 2001;Bischoff and Franzini-Armstrong, 2004). Interstitial "muscle-derived" stem cells give rise to several lineages after transplantation and in this setting, contribute to synchronized reconstitution of blood vessels (pericytes, smooth muscle cells [SMCs], and endothelial cells), peripheral nerve (Schwann cells), and muscle cells (myofibers and SCs; Tamaki et al., 2005). However, participation of multipotent interstitial stem cells in physiological muscle repair appears to be limited. Instead, it is widely accepted that sublaminal SCs represent the pre-eminent muscle stem cell type used for muscle growth, repair and regeneration (Dhawan...

Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells

“…In skeletal muscle, pericytes and satellite cells are often adjacent to each other 18 (arrows in the Fig. 1m); however, AP was never detected in Pax7 + or MyoD + satellite cells at any time examined; an example at P7 is shown in Supplementary Figure S1e,f, respectively.…”

BMP-9-induced muscle heterotopic ossification requires changes to the skeletal muscle microenvironment

“…Satellite cells, which are juxtaposed between the plasma membrane of the muscle fibers and the basement membrane, are known to provide a source of myogenic progenitor cells that contribute to lifetime muscle fiber repair, (18)(19)(20) whereas stromal progenitor cells (mrSCs), which reside in niches located between the muscle fibers, are closely associated with the vasculature. (21)(22)(23)26) Many markers are used to identify and enrich the mrSC population, the most common being Sca1. (21,23,26) This study showed, for the first time, that BMP-9 is able to induce the osteogenic differentiation program in primary mrSCs.…”

“…(18)(19)(20) The second source, muscle-resident mesenchymal or stromal cells (mrSCs), is located around blood vessels in the connective tissue compartment and is closely associated with satellite cells. (21)(22)(23) In culture, mrSCs are multipotent and can differentiate into many mesodermal cell lineages. (21,(23)(24)(25)(26) One important characteristic of mrSCs is their high immunoreactivity with anti-Sca1 antibody.…”

Les cellules du muscle chantent en chœur une berceuse pour cellules souches

“…Les cellules satellites sont localisées près des capillaires sanguins et nous avons montré in vitro que les cellules endothéliales (CE) et les mpc établissent des interactions paracrines privilégiées, stimulant la myogenèse pour les premières et l'angiogenèse pour les secondes, notamment via le VEGF (vascular endothelial growth factor) [8]. Un autre couple ligand-récepteur essentiel à la régulation de l'homéostasie vasculaire est celui que forme les angiopoïétines et le récepteur Tie-2.…”

“…Nos précédents travaux avaient montré que les cellules endothéliales stimulent la croissance des cellules myogéniques et que, inversement, les cellules myogéniques sont proangiogéniques. Le VEGF joue un rôle important dans cette relation bidirectionnelle [8]. On peut proposer que pendant la régénération musculaire, c'est-à-dire lorsque les vaisseaux ne sont pas stabilisés, les cellules endothéliales et myogéniques peuvent interagir entre elles pour promouvoir la myogenèse et l'angiogenèse.…”