A critical role for macrophages in neovessel formation and the development of stenosis in tissue‐engineered vascular grafts

Hibino, Narutoshi; Yi, Tai; Duncan, Daniel R.; Rathore, Animesh; Dean, Ethan W.; Naito, Yuji; Dardik, Alan; Kyriakides, Themis R.; Madri, Joseph A.; Pober, Jordan S.; Shinoka, Toshiharu; Breuer, Christopher K.

doi:10.1096/fj.11-186585

Cited by 207 publications

(255 citation statements)

References 39 publications

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“…Macrophages are likely associated with the early stages of inflammation-mediated TEVG remodeling leading to recruitment of aSMA + cells via paracrine mechanisms as in the mouse model. 31,32 At 24 weeks, there was complete recellularization with aSMA + cells and only rare CD45 + cells, consistent with the hypothesis that favorable remodeling coincides with the resolution of inflammation and an absence of immunogenicity of these grafts. Short TEVGs (2-3 cm) that were implanted interpositionally were used in these studies to evaluate graft remodeling as efficiently as possible.…”

supporting

confidence: 79%

Implantation of Completely Biological Engineered Grafts Following Decellularization into the Sheep Femoral Artery

Syedain

Meier

Lahti

et al. 2014

Tissue Engineering Part A

129

108

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The performance of completely biological, decellularized engineered allografts in a sheep model was evaluated to establish clinical potential of these unique arterial allografts. The 4-mm-diameter, 2-3-cm-long grafts were fabricated from fibrin gel remodeled into an aligned tissue tube in vitro by ovine dermal fibroblasts. Decellularization and subsequent storage had little effect on graft properties, with burst pressure exceeding 4000 mmHg and the same compliance as the ovine femoral artery. Grafts were implanted interpositionally in the femoral artery of six sheep (n = 9), with contralateral sham controls (n = 3). At 8 weeks (n = 5) and 24 weeks (n = 4), all grafts were patent and showed no evidence of dilatation or mineralization. Mid-graft lumen diameter was unchanged. Extensive recellularization occurred, with most cells expressing aSMA. Endothelialization was complete by 24 weeks with elastin deposition evident. These completely biological grafts possessed circumferential alignment/mechanical anisotropy characteristic of native arteries and were cultured only 5 weeks prior to decellularization and storage as ''off-the-shelf'' grafts.

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supporting

confidence: 79%

Implantation of Completely Biological Engineered Grafts Following Decellularization into the Sheep Femoral Artery

Syedain

Meier

Lahti

et al. 2014

Tissue Engineering Part A

129

108

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“…We discovered that the vascular neotissue formation is driven by migration of the host endothelial cells and smooth muscle cells (SMCs) from the neighboring blood vessel wall through an immune-mediated process orchestrated by the seeded cells using a paracrine mechanism. 9,10 So far, our studies have focused mainly on the cellular processes involved in vascular neotissue formation, less on formation of the extracellular matrix (ECM) and the associated biomechanical factors. [7][8][9][10] There is a growing literature highlighting the importance of mechanobiological principles on vascular physiology and pathophysiology.…”

mentioning

confidence: 99%

“…9,10 So far, our studies have focused mainly on the cellular processes involved in vascular neotissue formation, less on formation of the extracellular matrix (ECM) and the associated biomechanical factors. [7][8][9][10] There is a growing literature highlighting the importance of mechanobiological principles on vascular physiology and pathophysiology. [11][12][13][14][15] For example, compliance mismatch between a vascular graft and the native vessel into which it is implanted has been demonstrated to be a critical factor, leading at times to the formation of neointimal hyperplasia and stenosis.…”

mentioning

confidence: 99%

Beyond Burst Pressure: Initial Evaluation of the Natural History of the Biaxial Mechanical Properties of Tissue-Engineered Vascular Grafts in the Venous Circulation Using a Murine Model

Naito

Lee

et al. 2014

Tissue Engineering Part A

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We previously developed and validated a murine model for investigating neotissue formation in tissueengineered vascular grafts (TEVGs). Herein, we present the first longitudinal assessment of both the microstructural composition and the mechanical properties of a TEVG through the process of neovessel formation (total scaffold degradation). We show that when (poly)glycolic acid-based biodegradable scaffolds were used as inferior vena cava interposition grafts in mice, the evolving neovessel developed biaxial properties that approached those of the native vein within 24 weeks of implantation. Further, we found that these changes in biaxial properties related temporally to extracellular matrix production and remodeling, including deposition of collagen (types I and III), elastic fibers (elastin and fibrillin-1), and glycosaminoglycans in addition to changes in matrix metalloproteinase (MMP)-2 and -9 activity. Improving our understanding of the mechanobiological principles underlying vascular neotissue formation in TEVGs holds great promise for improving the design of TEVGs and enabling us to continue the translation of this technology from the bench to the clinic.

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“…10,11 In studies evaluating vascular neotissue formation in TEVG in animals that were macrophage depleted using clodronate liposomes, we demonstrated that 11 In this same study, we discovered that the macrophages infiltrating patent TEVG demonstrated a shift away from the M1 phenotype, while the macrophages infiltrating stenotic TEVG demonstrated increased expression of M1 phenotypic markers. We have also previously demonstrated that cell seeding is not essential for vascular neotissue formation, but instead functions to improve patency by modulating the host inflammatory response to the TEVG scaffold by decreasing the number infiltrating macrophages and shifting the macrophage phenotype away from M1 through an as yet undetermined paracrine mechanism.…”

Section: Discussionmentioning

confidence: 81%

Comparison of the Biological Equivalence of Two Methods for Isolating Bone Marrow Mononuclear Cells for Fabricating Tissue-Engineered Vascular Grafts

Kurobe

Tara

Maxfield

et al. 2015

Tissue Engineering Part C: Methods

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Our approach for fabricating tissue-engineered vascular grafts (TEVG), applied in the surgical management of congenital heart disease, is accomplished by seeding isolated bone marrow-derived mononuclear cells (BMMNCs) onto biodegradable scaffolds. The current method used for isolation of BM-MNCs is density centrifugation in Ficoll. This is a time-consuming, labor-intensive, and operator-dependent method. We previously demonstrated that a simpler, faster, and operator-independent method for isolating BM-MNCs using a filter elution technique was feasible. In this study, we compare the use of each technique to determine if the BMMNCs isolated by the filtration elution method are biologically equivalent to BM-MNCs isolated using density centrifugation. Scaffolds were constructed from a nonwoven poly(glycolic acid) fiber mesh coated with 50:50 poly(l-lactide-co-e-caprolactone) sealant. BM-MNCs were isolated from the bone marrow of syngeneic C57BL/6 mice by either density centrifugation with Ficoll or filtration (Ficoll vs. Filter), then statically seeded onto scaffolds, and incubated overnight. The TEVG were implanted in 10-week-old C57BL/6 mice (n = 23 for each group) as inferior vena cava interposition grafts and explanted at 14 days for analysis. At 14 days after implantation, there were no significant differences in graft patency between groups (Ficoll: 87% vs. Filter: 78%, p = 0.45). Morphometric analysis by hematoxylin and eosin staining showed no difference of graft luminal diameter or neointimal thickness between groups (luminal diameter, Ficoll: 620.3 -82.9 mm vs. Filter: 633.3 -131.0 mm, p = 0.72; neointimal thickness, Ficoll: 37.9 -7.8 mm vs. Filter: 37.9 -11.2 mm, p = 0.99). Histologic examination demonstrated similar degrees of cellular infiltration and extracellular matrix deposition, and endothelial cell coverage on the luminal surface, in either group. Macrophage infiltration showed no difference in the number of F4/80-positive cells or macrophage phenotypes between the two experimental groups (Ficoll: 2041 -1048 cells/mm 2 vs. Filter: 1887 -907.7 cells/mm 2 , p = 0.18). We confirmed the biological equivalence of BM-MNCs, isolated using either density centrifugation or filtration, for making TEVG.

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A critical role for macrophages in neovessel formation and the development of stenosis in tissue‐engineered vascular grafts

Cited by 207 publications

References 39 publications

Implantation of Completely Biological Engineered Grafts Following Decellularization into the Sheep Femoral Artery

Implantation of Completely Biological Engineered Grafts Following Decellularization into the Sheep Femoral Artery

Beyond Burst Pressure: Initial Evaluation of the Natural History of the Biaxial Mechanical Properties of Tissue-Engineered Vascular Grafts in the Venous Circulation Using a Murine Model

Comparison of the Biological Equivalence of Two Methods for Isolating Bone Marrow Mononuclear Cells for Fabricating Tissue-Engineered Vascular Grafts

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