Selective Activation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes Local Microvascular Network Growth

Sefcik, Lauren S.; Aronin, Caren E. Petrie; Awojoodu, Anthony O.; Shin, Soo Jung; Gabhann, Feilim Mac; Macdonald, Timothy L.; Wamhoff, Brian R.; Lynch, Kevin R.; Peirce, Shayn M.; Botchwey, Edward A.

doi:10.1089/ten.tea.2010.0404

Cited by 45 publications

(53 citation statements)

References 44 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regulating the secretion of these "angiocrine" factors may be critical to improving the treatment of ischemic tissue diseases and enhancing regenerative capacity of biomedical implant materials. Local activation of S1P receptors 1 and 3, with the synthetic S1P analog FTY720, enhances microvascular remodeling through expansion of arterioles and capillary networks (9). Modulation of S1P receptors on ECs may be a unique way to control the localization of circulating cells that contribute to tissue regeneration and wound healing.…”

mentioning

confidence: 99%

Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis

Awojoodu

Ogle

Sefcik

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

135

221

View full text Add to dashboard Cite

Endothelial cells play significant roles in conditioning tissues after injury by the production and secretion of angiocrine factors. At least two distinct subsets of monocytes, CD45 + CD11b + Gr1 + Ly6C + inflammatory and CD45 + CD11b + Gr1 − Ly6C − anti-inflammatory monocytes, respond differentially to these angiocrine factors and promote pathogen/debris clearance and arteriogenesis/tissue regeneration, respectively. We demonstrate here that local sphingosine 1-phosphate receptor 3 (S1P 3 ) agonism recruits anti-inflammatory monocytes to remodeling vessels. Poly(lactic-co-glycolic acid) thin films were used to deliver FTY720, an S1P 1/3 agonist, to inflamed and ischemic tissues, which resulted in a reduction in proinflammatory cytokine secretion and an increase in regenerative cytokine secretion. The altered balance of cytokine secretion results in preferential recruitment of antiinflammatory monocytes from circulation. The chemotaxis of these cells, which express more S1P 3 than inflammatory monocytes, toward SDF-1α was also enhanced with FTY720 treatment, but not in S1P 3 knockout cells. FTY720 delivery enhanced arteriolar diameter expansion and increased length density of the local vasculature. This work establishes a role for S1P receptor signaling in the local conditioning of tissues by angiocrine factors that preferentially recruit regenerative monocytes that can enhance healing outcomes, tissue regeneration, and biomaterial implant functionality.sphingolipid | microvascular remodeling | biomaterials | immunomodulation | tissue engineering

show abstract

mentioning

confidence: 99%

Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis

Awojoodu

Ogle

Sefcik

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

135

221

View full text Add to dashboard Cite

show abstract

“…Moreover, PNF1 treatment signifi cantly increased the diameters of local arterioles and venules. Similar effects can be observed by incorporation of sphingosine-1-phosphate (S1P) or S1P receptor-selective agonists into the PLGA (Sefcik et al, , 2011. Ibuprofen is a non-selective cyclooxygenase (COX) inhibitor, which is increasingly used as a pain-reducing component in modern wound dressings.…”

Section: Drug Delivery Systemsmentioning

confidence: 83%

The dorsal skinfold chamber: window into the dynamic interaction of biomaterials with their surrounding host tissue

Laschke

Vollmar²,

Menger³

2011

eCM

144

128

View full text Add to dashboard Cite

The implantation of biomaterials into the human body has become an indispensable part of almost all fi elds of modern medicine. Accordingly, there is an increasing need for appropriate approaches, which can be used to evaluate the suitability of different biomaterials for distinct clinical indications. The dorsal skinfold chamber is a sophisticated experimental model, which has been proven to be extremely valuable for the systematic in vivo analysis of the dynamic interaction of small biomaterial implants with the surrounding host tissue in rats, hamsters and mice. By means of intravital fl uorescence microscopy, this chronic model allows for repeated analyses of various cellular, molecular and microvascular mechanisms, which are involved in the early infl ammatory and angiogenic host tissue response to biomaterials during the initial 2-3 weeks after implantation. Therefore, the dorsal skinfold chamber has been broadly used during the last two decades to assess the in vivo performance of prosthetic vascular grafts, metallic implants, surgical meshes, bone substitutes, scaffolds for tissue engineering, as well as for locally or systemically applied drug delivery systems. These studies have contributed to identify basic material properties determining the biocompatibility of the implants and vascular ingrowth into their surface or internal structures. Thus, the dorsal skinfold chamber model does not only provide deep insights into the complex interactions of biomaterials with the surrounding soft tissues of the host but also represents an important tool for the future development of novel biomaterials aiming at an optimisation of their biofunctionality in clinical practice.

show abstract

“…33 Briefly, FTY720 and VPC01091 were chosen as S1P receptor-targeted drugs. Films were loaded with a loading ratio of 1:200 (wt./wt., drug:PLAGA).…”

Section: Fabrication Of Drug-loaded Plaga Thin Filmsmentioning

confidence: 99%

Abluminal Stimulation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes and Stabilizes Endothelial Sprout Formation

Das

Lenz

Awojoodu

et al. 2015

Tissue Engineering Part A

Self Cite

View full text Add to dashboard Cite

Local delivery of lipid mediators has become a promising new approach for therapeutic angiogenesis and regenerative medicine. In this study, we investigated how gradient stimulation (either abluminal/distal or luminal/ proximal) of engineered microvessels with sphingosine 1-phosphate (S1P) receptor-subtype-targeted molecules affects endothelial sprout growth using a microfluidic device. Our studies show that distal stimulation of microvessels with FTY720, an S1P1/3 selective agonist, promotes both arterial and venular sprout growth, whereas proximal stimulation does not. Using novel pharmacological antagonists of S1P receptor subtypes, we further show that S1P3 functionality is necessary for VEGF-induced sprouting, and confirmed these findings ex vivo using a murine aortic ring assay from S1P3-deficient mice. S1P3 agonist stimulation enhanced vascular stability in both cell types via upregulation of the interendothelial junction protein VE-cadherin. Lastly, S1P3 activation under flow promoted endothelial sprouting and branching while decreasing migratory cell fate in the microfluidic device. We used an in vivo murine dorsal skinfold window chamber model to confirm S1P3's role in neovascular branching. Together, these data suggest that a distal transendothelial gradient of S1P1/3-targeted drugs is an effective technique for both enhancing and stabilizing capillary morphogenesis in angiogenic applications.

show abstract

Selective Activation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes Local Microvascular Network Growth

Cited by 45 publications

References 44 publications

Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis

Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis

The dorsal skinfold chamber: window into the dynamic interaction of biomaterials with their surrounding host tissue

Abluminal Stimulation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes and Stabilizes Endothelial Sprout Formation

Contact Info

Product

Resources

About