Dataset Information

Matrix production and organization by endothelial colony forming cells in mechanically strained engineered tissue constructs.

ABSTRACT:

Aims

Tissue engineering is an innovative method to restore cardiovascular tissue function by implanting either an in vitro cultured tissue or a degradable, mechanically functional scaffold that gradually transforms into a living neo-tissue by recruiting tissue forming cells at the site of implantation. Circulating endothelial colony forming cells (ECFCs) are capable of differentiating into endothelial cells as well as a mesenchymal ECM-producing phenotype, undergoing Endothelial-to-Mesenchymal-transition (EndoMT). We investigated the potential of ECFCs to produce and organize ECM under the influence of static and cyclic mechanical strain, as well as stimulation with transforming growth factor ?1 (TGF?1).

Methods and results

A fibrin-based 3D tissue model was used to simulate neo-tissue formation. Extracellular matrix organization was monitored using confocal laser-scanning microscopy. ECFCs produced collagen and also elastin, but did not form an organized matrix, except when cultured with TGF?1 under static strain. Here, collagen was aligned more parallel to the strain direction, similar to Human Vena Saphena Cell-seeded controls. Priming ECFC with TGF?1 before exposing them to strain led to more homogenous matrix production.

Conclusions

Biochemical and mechanical cues can induce extracellular matrix formation by ECFCs in tissue models that mimic early tissue formation. Our findings suggest that priming with bioactives may be required to optimize neo-tissue development with ECFCs and has important consequences for the timing of stimuli applied to scaffold designs for both in vitro and in situ cardiovascular tissue engineering. The results obtained with ECFCs differ from those obtained with other cell sources, such as vena saphena-derived myofibroblasts, underlining the need for experimental models like ours to test novel cell sources for cardiovascular tissue engineering.

SUBMITTER: de Jonge N

PROVIDER: S-EPMC3759389 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Matrix production and organization by endothelial colony forming cells in mechanically strained engineered tissue constructs.

de Jonge Nicky N Muylaert Dimitri E P DE Fioretta Emanuela S ES Baaijens Frank P T FP Fledderus Joost O JO Verhaar Marianne C MC Bouten Carlijn V C CV

PloS one 20130902 9

<h4>Aims</h4>Tissue engineering is an innovative method to restore cardiovascular tissue function by implanting either an in vitro cultured tissue or a degradable, mechanically functional scaffold that gradually transforms into a living neo-tissue by recruiting tissue forming cells at the site of implantation. Circulating endothelial colony forming cells (ECFCs) are capable of differentiating into endothelial cells as well as a mesenchymal ECM-producing phenotype, undergoing Endothelial-to-Mesen ...[more]

PMID: 24023827

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Project description:Artificial small-diameter vascular grafts remain an unmet need in modern medicine, due to the thrombosis and neointimal hyperplasia that plague currently available synthetic devices. Tissue engineering techniques, including in vitro endothelialization, could offer a solution to this problem. A potential minimally invasive source of patient autologous endothelium is endothelial colony-forming cells (ECFCs), endothelial-like outgrowth products of circulating progenitors. While ECFCs respond to shear stress similar to mature endothelial cells (ECs), their response to luminal topographic micropatterning (TMP), a biomaterial modification with the potential to flow-independently, enhance the attachment, migration, gene expression, and function of mature ECs, remains unstudied. In this study, case-matched carotid endothelial cells (CaECs) and blood-derived ECFCs are statically cultured on polyurethane substrates with micropatterned pitches (pitch = peak to peak distance) ranging from 3-to 14 μm. On all pattern pitches tested, both CaECs and ECFCs showed significant and robust alignment to the angle of the micropatterns. Using a novel cell-by-cell image analysis technique, it was found that actin fibers similarly and significantly aligned to the angle of micropatterned features on all pitches tested. Microtubules analyzed through the same novel approach showed significant alignment on most pitches examined, with a greater variation in fiber angle overall. Interestingly, only CaECs showed significant cellular elongation, and notably to a lower degree than previously seen either in vivo due to flow or in vitro due to spatial growth restriction micropatterning, but consistent with earlier studies of TMP. Neither cell type displayed any significant micropattern-driven changes in the expression of KLF-2 or the downstream adhesion molecules it regulates. These results demonstrate that TMP flow-independently affects ECFC morphology, but that alignment alone is insufficient to drive protective changes in EC and ECFC function.

Project description:BackgroundSuccessful pregnancies are nowadays possible after kidney transplantation but are associated with a higher incidence of maternal and fetal complications. Immunosuppressive therapy causes cardiovascular side effects but must be maintained during pregnancy. Little is known about the consequences of maternal kidney transplantation on offspring's endothelial health. Endothelial colony forming cells (ECFCs) represent a highly proliferative subtype of endothelial progenitor cells and are crucial for vascular homeostasis, repair and neovascularization. Therefore, we investigated whether maternal kidney transplantation affects fetal ECFCs' characteristics.MethodsECFCs were isolated from umbilical cord blood of uncomplicated and post-kidney-transplant pregnancies and analyzed for their functional abilities with proliferation, cell migration, centrosome orientation and angiogenesis assays. Further, ECFCs from uncomplicated pregnancies were exposed to either umbilical cord serum from uncomplicated or post-kidney-transplant pregnancies.ResultsPost-kidney-transplant ECFCs showed significantly less proliferation, less migration and less angiogenesis compared to control ECFCs. The presence of post-kidney-transplant umbilical cord serum led to similar functional aberrations of ECFCs from uncomplicated pregnancies.ConclusionsThese pilot data demonstrate differences in ECFCs' biological characteristics in offspring of women after kidney transplantation. Further studies are needed to monitor offspring's long-term cardiovascular development and to assess possible causal relationships with immunosuppressants, uremia and maternal cardiovascular alterations.ImpactPregnancy after kidney transplantation has become more common in the past years but is associated with higher complications for mother and offspring. Little is known of the impact of maternal kidney transplantation and the mandatory immunosuppressive therapy on offspring vascular development. In this study we are the first to address and detect an impairment of endothelial progenitor cell function in offspring of kidney-transplanted mothers. Serum from post-transplant pregnancies also causes negative effects on ECFCs' function. Clinical studies should focus on long-term monitoring of offspring's cardiovascular health.

Dataset Information

Matrix production and organization by endothelial colony forming cells in mechanically strained engineered tissue constructs.

Aims

Methods and results

Conclusions

Publications

Matrix production and organization by endothelial colony forming cells in mechanically strained engineered tissue constructs.

Similar Datasets

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