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Engineered microvessels with strong alignment and high lumen density via cell-induced fibrin gel compaction and interstitial flow.

ABSTRACT: The development of engineered microvessels with clinically relevant characteristics is a critical step toward the creation of engineered myocardium. Alignment is one such characteristic that must be achieved, as it both mimics native capillary beds and provides natural inlet and outlet sides for perfusion. A second characteristic that is currently deficient is cross-sectional lumen density, typically under 100 lumens/mm²; the equivalent value for human myocardium is 2000 lumens/mm². Therefore, this study examined the effects of gel compaction and interstitial flow on microvessel alignment and lumen density. Strong microvessel alignment was achieved via mechanically constrained cell-induced fibrin gel compaction following vasculogenesis, and high lumen density (650 lumens/mm²) was achieved by the subsequent application of low levels of interstitial flow. Low interstitial flow also conferred microvessel barrier function.

SUBMITTER: Morin KT

PROVIDER: S-EPMC3926183 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Engineered microvessels with strong alignment and high lumen density via cell-induced fibrin gel compaction and interstitial flow.

Morin Kristen T KT Dries-Devlin Jessica L JL Tranquillo Robert T RT

Tissue engineering. Part A 20131114 3-4

The development of engineered microvessels with clinically relevant characteristics is a critical step toward the creation of engineered myocardium. Alignment is one such characteristic that must be achieved, as it both mimics native capillary beds and provides natural inlet and outlet sides for perfusion. A second characteristic that is currently deficient is cross-sectional lumen density, typically under 100 lumens/mm²; the equivalent value for human myocardium is 2000 lumens/mm². Therefore, t ...[more]

PMID: 24083839

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Project description:Different tissue-engineering approaches have been developed to induce and promote cardiac regeneration; however, the impact of the immune system and its responses to the various scaffold components of the engineered grafts remains unclear. Fibrin-based engineered heart tissue (EHT) was generated from neonatal Lewis (Lew) rat heart cells and transplanted onto the left ventricular surface of three different rat strains: syngeneic Lew, allogeneic Brown Norway, and immunodeficient Rowett Nude rats. Interferon spot frequency assay results showed similar degrees of systemic immune activation in the syngeneic and allogeneic groups, whereas no systemic immune response was detectable in the immunodeficient group (p < .001 vs. syngeneic and allogeneic). Histological analysis revealed much higher local infiltration of CD3- and CD68-positive cells in syngeneic and allogeneic rats than in immunodeficient animals. Enzyme-linked immunospot and immunofluorescence experiments revealed matrix-directed TH1-based rejection in syngeneic recipients without collateral impairment of heart cell survival. Bioluminescence imaging was used for in vivo longitudinal monitoring of transplanted luciferase-positive EHT constructs. Survival was documented in syngeneic and immunodeficient recipients for a period of up to 110 days after transplant, whereas in the allogeneic setting, graft survival was limited to only 14 ± 1 days. EHT strategies using autologous cells are promising approaches for cardiac repair applications. Although fibrin-based scaffold components elicited an immune response in our studies, syngeneic cells carried in the EHT were relatively unaffected.An initial insight into immunological consequences after transplantation of engineered heart tissue was gained through this study. Most important, this study was able to demonstrate cell survival despite rejection of matrix components. Generation of syngeneic human engineered heart tissue, possibly using human induced pluripotent stem cell technology with subsequent directed rejection of matrix components, may be a potential future approach to replace diseased myocardium.

Dataset Information

Engineered microvessels with strong alignment and high lumen density via cell-induced fibrin gel compaction and interstitial flow.

Publications

Engineered microvessels with strong alignment and high lumen density via cell-induced fibrin gel compaction and interstitial flow.

Similar Datasets

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