Quantification of Total and Perfused Blood Vessels in Murine Skin Autografts Using a Fluorescent Double-Labeling Technique

O’Ceallaigh, Siobhan; Herrick, Sarah E.; Bluff, Joanne E.; McGrouther, Duncan Angus; Ferguson, Mark W. J.

doi:10.1097/01.prs.0000185611.87601.b8

Cited by 48 publications

(29 citation statements)

References 23 publications

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“…Reperfusion appeared to occur in an all-or-none pattern consistent with the mechanism of donor vascular network reconnection to recipient vessels. Though this has not been previously studied in orthotopic tracheal grafts, other studies have demonstrated similar mechanics of revascularization as well as time course in avascular grafts such as skin autografts (19,20) and peripheral nerve allografts (21). Interestingly, the transgenic Tie2/β-galactosidase recipients had many cells in the allograft expressing β-galactosidase.…”

Section: Figurementioning

confidence: 88%

Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis

Babu¹,

Murakawa²,

Thurman³

et al. 2007

J. Clin. Invest.

112

165

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Small airway fibrosis (bronchiolitis obliterans syndrome) is the primary obstacle to long-term survival following lung transplantation. Here, we show the importance of functional microvasculature in the prevention of epithelial loss and fibrosis due to rejection and for the first time, relate allograft microvascular injury and loss of tissue perfusion to immunotherapy-resistant rejection. To explore the role of alloimmune rejection and airway ischemia in the development of fibroproliferation, we used a murine orthotopic tracheal transplant model. We determined that transplants were reperfused by connection of recipient vessels to donor vessels at the surgical anastomosis site. Microcirculation through the newly formed vascular anastomoses appeared partially dependent on VEGFR2 and CXCR2 pathways. In the absence of immunosuppression, the microvasculature in rejecting allografts exhibited vascular complement deposition, diminished endothelial CD31 expression, and absent perfusion prior to the onset of fibroproliferation. Rejecting grafts with extensive endothelial cell injury were refractory to immunotherapy. After early microvascular loss, neovascularization was eventually observed in the membranous trachea, indicating a reestablishment of graft perfusion in established fibrosis. One implication of this study is that bronchial artery revascularization at the time of lung transplantation may decrease the risk of subsequent airway fibrosis.

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Section: Figurementioning

confidence: 88%

Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis

Babu¹,

Murakawa²,

Thurman³

et al. 2007

J. Clin. Invest.

112

165

View full text Add to dashboard Cite

show abstract

“…Early revascularization is attributable to newly formed vascular anastomoses between graft and recipient wound bed vessels; this occurs mainly in the central portion of the recipient bed and graft [32]. It would also be important to distinguish the participation of preexisting versus newly formed vessels in this model.…”

Section: Discussionmentioning

confidence: 98%

“…1C; 7.4 ± 2.5 vessels/cm 2 vs. 2.3 ± 0.8 vessels/cm 2 ; n = 12; P \ 0.001). It is important to note that full-thickness skin grafts revascularize primarily from the graft edges, unlike split-thickness grafts, which have been shown to revascularize not only from the graft edges but also from the underlying recipient wound bed [8,32]. Also, the hypodermal/adipose dermis/fascial fat layer (adipose dermis) and panniculus carnosus were all removed from the donor skin graft prior to transplantation.…”

Section: Eswt Enhances Ischemic Tissue Angiogenesis and Revascularizamentioning

confidence: 99%

Angiogenic response to extracorporeal shock wave treatment in murine skin isografts

et al. 2008

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Skin grafts are commonly utilized and proven effective methods of open wound coverage. Revascularization through neoangiogenesis is a pivotal mechanism for skin graft integration and durability. Extracorporeal shock-wave treatment (ESWT) has been demonstrated to accelerate wound repair; however, its mechanism-of-action is unclear. We investigated the role of ESWT in early revascularization of full-thickness skin isografts in a murine model. Cohorts of mice were euthanized and skin grafts were harvested 6 h, 2, 4, and 7 days post grafting +/- ESWT. Various aspects of graft neovascularization were measured including gross morphology, quantitative microscopy (vessel number, density), immunohistochemistry (CD31), cDNA SuperArrays for 84 angiogenesis-specific genes, and custom-designed 'Wound Repair' TaqMan Low Density Array (TLDA) cards to assess expression of 188 wound repair genes. We demonstrate that a single administration of ESWT immediately following skin grafting significantly enhances recipient graft revascularization (increased vessel number, size, and density). An augmented early pro-angiogenic and suppressed delayed pro-inflammatory response to ESWT was accompanied by significantly increased expression of both skin graft CD31 and angiogenesis pathway-specific genes, including ELR-CXC chemokines (CXCL1, CXCL2, CXCL5), CC chemokines (CCL2, CCL3, CCL4), cytokines (IL-1 beta, IL-6, G-CSF, VEGF-A), matrix metalloproteinases (MMP3, MMP9, MMP13), hypoxia-inducible factors (HIF-1 alpha), and vascular remodeling kinase (Mst1), as early as 6 h and up to 7 days post grafting and treatment. These findings suggest that early pro-angiogenic and anti-inflammatory effects of ESWT promote tissue revascularization and wound healing by augmenting angiogenesis and dampening inflammation.

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“…10 In contrast, previous studies suggested that graft vessels may degenerate after reperfusion, leaving the basement membrane as a potential conduit for further vessel ingrowth. [11][12][13] Therefore, it was the aim of this study to gain further insight into the morphology and development of the vascular structures within the skin graft after reperfusion and to three-dimensionally visualize its capillary network.…”

mentioning

confidence: 99%

Temporary Angiogenic Transformation of the Skin Graft Vasculature after Reperfusion

Lindenblatt¹,

Platz

Althaus

et al. 2010

Plastic and Reconstructive Surgery

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The authors were able to show for the first time a temporary angiogenic response within the capillaries of the skin graft. This most likely represents a reaction to reperfusion allowing the supply of proangiogenic factors to the hypoxic skin graft. The detection of an angiogenic response within the graft capillaries is for the first time made possible in the newly developed model and is therefore completely novel.

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Quantification of Total and Perfused Blood Vessels in Murine Skin Autografts Using a Fluorescent Double-Labeling Technique

Cited by 48 publications

References 23 publications

Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis

Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis

Angiogenic response to extracorporeal shock wave treatment in murine skin isografts

Temporary Angiogenic Transformation of the Skin Graft Vasculature after Reperfusion

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