Abstract 317: Paracrine Effects of Satellite Cells on Collateral Vessel Formation

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Laura Hansen ◽  
Giji Joseph ◽  
Daiana Weiss ◽  
W. Robert Taylor
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Satellite Cells ◽  
Peripheral Artery ◽  
Collateral Vessel ◽  
Paracrine Effects ◽  
Vessel Formation ◽  
Collateral Growth ◽  
Artery Disease

Peripheral artery disease is a major health problem in the United States that effects 8.5 million people and can lead to limb pain, decreased mobility, and in severe cases amputation. The ability to form a robust collateral network to restore blood flow and prevent ischemia leads to a better prognosis and restoration of function. The growth of collaterals is a complex process that involves recruitment of various cell types including smooth muscle cells, endothelial cells, and macrophages. Migration and proliferation of these cells are processes regulated by numerous cytokine and paracrine signals. We hypothesize that an important and novel source of these signals is satellite cells. Satellite cells are myogenic progenitor cells that lie below the basal lamina of muscle fibers. In healthy muscle, the cells are quiescent but in response to injury, such as ischemia, they become activated and proliferate. We hypothesized that activated satellite cells produce factors that will influence critical cells for vessel formation in addition to differentiating to repair muscle. To study the paracrine effects of satellite cells on vascular smooth muscle cells, we used a co-culture system with freshly isolated satellite cells from the ischemic leg as the stimulus. We found that satellite cells significantly increased smooth muscle migration 2.5 fold compared to media alone using a modified Boyden chamber assay. BrdU staining to assess proliferation showed modest increases in smooth muscle proliferation (1.3 fold change, p<0.01). Finally, to investigate these paracrine effects in vivo, we delivered alginate encapsulated satellite cells to mice following the hind limb ischemia procedure, which is a model of collateral growth. We found that mice that received the encapsulated satellite cells had significantly improved perfusion as measured by Laser Doppler imaging at day 14 post surgery when compared to empty capsules (perfusion ratio of 0.87 ± 0.04 (cells) vs 0.68 ± 0.07 (empty capsules), p<0.05). This result demonstrates that satellite cells can positively influence collateral growth in vivo. We believe that satellite cells play a critical role in collateral vessel formation and may potentially be a therapeutic strategy for the treatment of peripheral artery disease.

Abstract 317: Satellite Cells Influence Collateral Vessel Formation via Paracrine Effects

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Laura Hansen ◽  
Wenxue Liu ◽  
Giji Joseph ◽  
Daiana Weiss ◽  
W. Robert Taylor
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Satellite Cells ◽  
Critical Role ◽  
Fold Increase ◽  
Endothelial Cell Migration ◽  
Collateral Vessel ◽  
Paracrine Factors ◽  
Artery Disease

Satellite cells are myogenic cells that play a critical role in skeletal muscle repair. They serve as stem cells for muscles, remaining dormant in healthy muscle but activating upon injury resulting in increased proliferation and differentiation into myoblasts. Another key aspect of muscle regeneration is reestablishing vascular supply, but the role of satellite cells in this process is not well established though they are known to produce a number of potential paracrine signals. Thus we hypothesized that satellite cells promote vascular growth through paracrine signaling induced by activation following muscle injury or ischemic damage from diseases such as peripheral artery disease. Using a murine model of hind limb ischemia, we showed that satellite cells increased 3.4 fold (p<0.01) in response to ischemia. To determine if satellite cells produce paracrine factors, we used a co-culture system for migration and proliferation. Satellite cells freshly isolated from the ischemic limb led to a 3.5 fold increase in smooth muscle migration (p<0.0001) and a 1.3 fold increase (p<0.01) in smooth muscle proliferation. Additionally, cultured satellite cells increased endothelial cell migration 2.8 fold. These results demonstrate the satellite cells produce paracrine factors which can drive both smooth muscle and endothelial cell migration and proliferation which are required for the development of collateral vessels. To test the potential therapeutic capability of satellite cells, alginate encapsulated satellite cells were delivered in the hind limb ischemic model. Using a whole animal in vivo imager to track luciferase expression of the cells, we found the encapsulated cells were viable for up to 2 weeks. The mice that received satellite cells also had significantly increased perfusion (28%, p<0.05) at 2 weeks as measured by Laser Doppler imaging. In conclusion our studies have shown that satellite cells increase in response to ischemia, produce paracrine factors that increase vascular cell migration in vitro, and lead to functional increases in perfusion in vivo. We believe these results demonstrate the critical role satellite cells play in collateral vessel formation and may be a potential new therapeutic approach for treating peripheral artery disease.

scholarly journals Development of an Exercise Training Protocol to Investigate Arteriogenesis in a Murine Model of Peripheral Artery Disease

2019 ◽  
Vol 20 (16) ◽  
pp. 3956 ◽  
Author(s):  
Ayko Bresler ◽  
Johanna Vogel ◽  
Daniel Niederer ◽  
Daphne Gray ◽  
Thomas Schmitz-Rixen ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Suitable Model ◽  
Peripheral Artery ◽  
Running Wheel ◽  
Limb Perfusion ◽  
Collateral Growth ◽  
Artery Disease ◽  
Set Up ◽  
Exercise Induced ◽  
And Control

Exercise is a treatment option in peripheral artery disease (PAD) patients to improve their clinical trajectory, at least in part induced by collateral growth. The ligation of the femoral artery (FAL) in mice is an established model to induce arteriogenesis. We intended to develop an animal model to stimulate collateral growth in mice through exercise. The training intensity assessment consisted of comparing two different training regimens in C57BL/6 mice, a treadmill implementing forced exercise and a free-to-access voluntary running wheel. The mice in the latter group covered a much greater distance than the former pre- and postoperatively. C57BL/6 mice and hypercholesterolemic ApoE-deficient (ApoE−/−) mice were subjected to FAL and had either access to a running wheel or were kept in motion-restricting cages (control) and hind limb perfusion was measured pre- and postoperatively at various times. Perfusion recovery in C57BL/6 mice was similar between the groups. In contrast, ApoE−/− mice showed significant differences between training and control 7 d postoperatively with a significant increase in pericollateral macrophages while the collateral diameter did not differ between training and control groups 21 d after surgery. ApoE−/− mice with running wheel training is a suitable model to simulate exercise induced collateral growth in PAD. This experimental set-up may provide a model for investigating molecular training effects.

scholarly journals Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 66-76 ◽  
Author(s):  
MC Galmiche ◽  
VE Koteliansky ◽  
J Briere ◽  
P Herve ◽  
P Charbord
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Stromal Cells ◽  
Muscle Cells ◽  
Mesenchymal Cells ◽  
Myoid Cells ◽  
Marrow Cultures

In human long-term marrow cultures connective tissue-forming stromal cells are an essential cellular component of the adherent layer where granulomonocytic progenitors are generated from week 2 onward. We have previously found that most stromal cells in confluent cultures were stained by monoclonal antibodies directed against smooth muscle- specific actin isoforms. The present study was carried out to evaluate the time course of alpha-SM-positive stromal cells and to search for other cytoskeletal proteins specific for smooth muscle cells. It was found that the expression of alpha-SM in stromal cells was time dependent. Most of the adherent spindle-shaped, vimentin-positive stromal cells observed during the first 2 weeks of culture were alpha- SM negative. On the contrary, from week 3 to week 7, most interdigitated stromal cells contained stress fibers whose backbone was made of alpha-SM-positive microfilaments. In addition, in confluent cultures, other proteins specific for smooth muscle were detected: metavinculin, h-caldesmon, smooth muscle myosin heavy chains, and calponin. This study confirms the similarity between stromal cells and smooth muscle cells. Moreover, our results reveal that cells in vivo with the phenotype closest to that of stromal cells are immature fetal smooth muscle cells and subendothelial intimal smooth muscle cells; a cell subset with limited development following birth but extensively recruited in atherosclerotic lesions. Stromal cells very probably derive from mesenchymal cells that differentiate along this distinctive vascular smooth muscle cell pathway. In humans, this differentiation seems crucial for the maintenance of granulomonopoiesis. These in vitro studies were completed by examination of trephine bone marrow biopsies from adults without hematologic abnormalities. These studies revealed the presence of alpha-SM-positive cells at diverse locations: vascular smooth muscle cells in the media of arteries and arterioles, pericytes lining capillaries, myoid cells lining sinuses at the abluminal side of endothelial cells or found within the hematopoietic logettes, and endosteal cells lining bone trabeculae. More or less mature cells of the granulocytic series were in intimate contact with the thin cytoplasmic extensions of myoid cells. Myoid cells may be the in vivo counterpart of stromal cells with the above-described vascular smooth muscle phenotype.

scholarly journals Induction of cyclooxygenase-2 in rat vascular smooth muscle cells in vitro and in vivo.

1994 ◽  
Vol 269 (11) ◽  
pp. 8504-8509
Author(s):  
K.A. Pritchard ◽  
M.K. O'Banion ◽  
J.M. Miano ◽  
N. Vlasic ◽  
U.G. Bhatia ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cyclooxygenase 2
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