Prevascularization of a Fibrin-Based Tissue Construct Accelerates the Formation of Functional Anastomosis with Host Vasculature

Chen, Xiaofang; Aledia, Anna S.; Ghajar, Cyrus M.; Griffith, Craig K.; Putnam, Andrew J.; Hughes, Christopher C.W.; George, Steven C.

doi:10.1089/ten.tea.2008.0314

Cited by 281 publications

(285 citation statements)

References 33 publications

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“…23 ECs and fibroblasts were suspended in a 10 mg=mL fibrinogen solution. The cell solutions were then mixed with thrombin at a concentration of 2 units=mL.…”

Section: Assembling Of Three-dimensional Prevascularized Tissue Constmentioning

confidence: 99%

“…Total vessel length=mm 2 , total number of continuous vessel networks=mm 2 , average length of vessel network, and average number of branches=vessel network were quantified as previously described. 23 …”

Section: Immunofluorescent Staining Of Whole Tissuementioning

confidence: 99%

“…23 The internal dimensions of the PDMS were 2 mm in height and 10 mm in diameter. In this geometry, delivery of nutrients was limited to only one surface making the effective thickness of the tissue 4 mm.…”

Section: Implantation Of the Prevascularized Tissue Constructsmentioning

confidence: 99%

“…23 The objective of our current study was to significantly accelerate the anatomosis of the implanted vessel network by using EPCs and manipulating stromal cell density. We demonstrate that tissues developed for 7 days in vitro with ECs derived from EPCs and a high density of fibroblasts are more mature (as evidenced by enhanced association of a-smooth muscle actin [a-SMA]-positive cells with the capillaries) and anastomose with the host circulation as early as 1 day (27 h) postimplantation.…”

Section: Introductionmentioning

confidence: 99%

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Rapid Anastomosis of Endothelial Progenitor Cell–Derived Vessels with Host Vasculature Is Promoted by a High Density of Cotransplanted Fibroblasts

Chen

Aledia

Popson

et al. 2010

Tissue Engineering Part A

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To ensure survival of engineered implantable tissues thicker than approximately 2-3 mm, convection of nutrients and waste products to enhance the rate of transport will be required. Creating a network of vessels in vitro, before implantation (prevascularization), is one potential strategy to achieve this aim. In this study, we developed three-dimensional engineered vessel networks in vitro by coculture of endothelial cells (ECs) and fibroblasts in a fibrin gel for 7 days. Vessels formed by cord blood endothelial progenitor cell-derived ECs (EPC-ECs) in the presence of a high density of fibroblasts created an interconnected tubular network within 4 days, compared with 5-7 days in the presence of a low density of fibroblasts. Vessels derived from human umbilical vein ECs (HUVECs) in vitro showed similar kinetics. Implantation of the prevascularized tissues into immunecompromised mice, however, revealed a dramatic difference in the ability of EPC-ECs and HUVECs to form anastomoses with the host vasculature. Vascular beds derived from EPC-ECs were perfused within 1 day of implantation, whereas no HUVEC vessels were perfused at day 1. Further, while almost 90% of EPC-EC-derived vascular beds were perfused at day 3, only one-third of HUVEC-derived vascular beds were perfused. In both cases, a high density of fibroblasts accelerated anastomosis by 2-3 days. We conclude that both EPC-ECs and a high density of fibroblasts significantly accelerate the rate of functional anastomosis, and that prevascularizing an engineered tissue may be an effective strategy to enhance convective transport of nutrients in vivo.

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“…23 ECs and fibroblasts were suspended in a 10 mg=mL fibrinogen solution. The cell solutions were then mixed with thrombin at a concentration of 2 units=mL.…”

Section: Assembling Of Three-dimensional Prevascularized Tissue Constmentioning

confidence: 99%

Section: Immunofluorescent Staining Of Whole Tissuementioning

confidence: 99%

Section: Implantation Of the Prevascularized Tissue Constructsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rapid Anastomosis of Endothelial Progenitor Cell–Derived Vessels with Host Vasculature Is Promoted by a High Density of Cotransplanted Fibroblasts

Chen

Aledia

Popson

et al. 2010

Tissue Engineering Part A

Self Cite

183

193

View full text Add to dashboard Cite

show abstract

“…For example, anastomosis of the developed vascular structures with the host vasculature following in vivo implantation may warrant such studies. 29 Alternatively, the development of tumors-on-a-chip strategies may be ideal to test the efficacy and negative side effects of therapeutic strategies. 30 In particular, such a platform could help to optimize important aspects of antiangiogenic therapies ranging from the development of the drug itself to the actual treatment of patients (e.g., chemical efficacy, choice of delivery vehicle, appropriate temporal profile of delivery, intratumoral localization of the drug, and efficacy of normalization of low quality vessels 5 ).…”

Section: Future Perspectivesmentioning

confidence: 99%