RETRACTED: Vascularised human tissue models: A new approach for the refinement of biomedical research

Schanz, Johanna; Pusch, Jacqueline; Hansmann, Jan; Walles, Heike

doi:10.1016/j.jbiotec.2010.03.015

Cited by 73 publications

(64 citation statements)

References 11 publications

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“…One of the focuses of our group is the creation of in vitro test models with our biological vascularized scaffold (BioVaSc) 2,3 . The BioVaSc can be used as a static or dynamic 3D matrix system.…”

Section: Introductionmentioning

confidence: 99%

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Tissue Engineering of a Human 3D <em>in vitro</em> Tumor Test System

Moll

Reboredo

Schwarz

et al. 2013

JoVE

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Cancer is one of the leading causes of death worldwide. Current therapeutic strategies are predominantly developed in 2D culture systems, which inadequately reflect physiological conditions in vivo. Biological 3D matrices provide cells an environment in which cells can self-organize, allowing the study of tissue organization and cell differentiation. Such scaffolds can be seeded with a mixture of different cell types to study direct 3D cell-cell-interactions. To mimic the 3D complexity of cancer tumors, our group has developed a 3D in vitro tumor test system. Our 3D tissue test system models the in vivo situation of malignant peripheral nerve sheath tumors (MPNSTs), which we established with our decellularized porcine jejunal segment derived biological vascularized scaffold (BioVaSc). In our model, we reseeded a modified BioVaSc matrix with primary fibroblasts, microvascular endothelial cells (mvECs) and the S462 tumor cell line. For static culture, the vascular structure of the BioVaSc is removed and the remaining scaffold is cut open on one side (Small Intestinal Submucosa SIS-Muc). The resulting matrix is then fixed between two metal rings (cell crowns).Another option is to culture the cell-seeded SIS-Muc in a flow bioreactor system that exposes the cells to shear stress. Here, the bioreactor is connected to a peristaltic pump in a self-constructed incubator. A computer regulates the arterial oxygen and nutrient supply via parameters such as blood pressure, temperature, and flow rate. This setup allows for a dynamic culture with either pressure-regulated pulsatile or constant flow.In this study, we could successfully establish both a static and dynamic 3D culture system for MPNSTs. The ability to model cancer tumors in a more natural 3D environment will enable the discovery, testing, and validation of future pharmaceuticals in a human-like model.

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Section: Introductionmentioning

confidence: 99%

“…The restored tubular vascular structures can subsequently be reseeded with human microvascular endothelial cells using a recirculation perfusion bioreactor . In the following step, the surface of the former lumen (mucosa) can be seeded with primary human cells to establish co-cultures 3,7,8 .…”

Section: Introductionmentioning

confidence: 99%

Tissue Engineering of a Human 3D <em>in vitro</em> Tumor Test System

Moll

Reboredo

Schwarz

et al. 2013

JoVE

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“…Hackmann and Redelmeier have found out in 2006 that 92 percent of the new drugs fail in clinical studies although the animal experiments were successful (Hackam & Redelmeier, 2006; as cited in Schanz et al, 2010). And it is not least for ethical reasons that suitable alternatives should be found for animal experiments.…”

Section: Engineered Tumor Tissues For Applied Researchmentioning

confidence: 99%

Three Dimensional Tissue Models for Research in Oncology

Nietzer¹,

Dandekar²,

Wasik³

et al. 2012

Selected Topics in Plastic Reconstructive Surgery

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“…2 A disadvantage of tissue slices is that they have a limited lifespan, making chronic and dose-response studies difficult. 3,4 Therefore, tissue-engineering methods that generate complex tissue models represent a promising alternative to tissue slices and may help in increasing the prediction of certain endpoints. Tissue engineering involves the creation of tissues by combining scaffolds and cells.…”

Section: Introductionmentioning

confidence: 99%

“…11 There are reports of decellularization methods for various organs and tissues, including the liver, 12,13 lung, 14 kidney, 15 heart, 16 muscle, 17 intestine, 18 and trachea. 10 These scaffolds could be reseeded with various cell types such as, for example, human liver cells 3,19 or Caco-2 3,18 to create human tissue models. Significantly, all these models depend on a sufficient oxygen and nutrient supply and, generally, engineered tissues tend to have poor and insufficient medium supply which supports tissue cell survival in deeper layers of the scaffolds and maintains phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Upcyte^®Microvascular Endothelial Cells Repopulate Decellularized Scaffold

Scheller

Dally²,

Hartmann³

et al. 2013

Tissue Engineering Part C: Methods

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A general problem in tissue engineering is the poor and insufficient blood supply to guarantee tissue cell survival as well as physiological tissue function. To address this limitation, we have developed an in vitro vascularization model in which a decellularized porcine small bowl segment, representing a capillary network within a collagen matrix (biological vascularized scaffold [BioVaSc]), is reseeded with microvascular endothelial cells (mvECs). However, since the supply of mvECs is limited, in general, and as these cells rapidly dedifferentiate, we have applied a novel technology, which allows the generation of large batches of quasi-primary cells with the ability to proliferate, whilst maintaining their differentiated functionality. These so called upcyte mvECs grew for an additional 15 population doublings (PDs) compared to primary cells. Upcyte mvECs retained endothelial characteristics, such as von Willebrandt Factor (vWF), CD31 and endothelial nitric oxide synthase (eNOS) expression, as well as positive Ulex europaeus agglutinin I staining. Upcyte mvECs also retained biological functionality such as tube formation, cell migration, and low density lipoprotein (LDL) uptake, which were still evident after PD27. Initial experiments using MTT and Live/Dead staining indicate that upcyte mvECs repopulate the BioVaSc Scaffold. As with conventional cultures, these cells also express key endothelial molecules (vWF, CD31, and eNOS) in a custom-made bioreactor system even after a prolonged period of 14 days. The combination of upcyte mvECs and the BioVaSc represents a novel and promising approach toward vascularizing bioreactor models which can better reflect organs, such as the liver.

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RETRACTED: Vascularised human tissue models: A new approach for the refinement of biomedical research

Cited by 73 publications

References 11 publications

Tissue Engineering of a Human 3D <em>in vitro</em> Tumor Test System

Tissue Engineering of a Human 3D <em>in vitro</em> Tumor Test System

Three Dimensional Tissue Models for Research in Oncology

Upcyte^®Microvascular Endothelial Cells Repopulate Decellularized Scaffold

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RETRACTED: Vascularised human tissue models: A new approach for the refinement of biomedical research

Cited by 73 publications

References 11 publications

Tissue Engineering of a Human 3D <em>in vitro</em> Tumor Test System

Tissue Engineering of a Human 3D <em>in vitro</em> Tumor Test System

Three Dimensional Tissue Models for Research in Oncology

Upcyte®Microvascular Endothelial Cells Repopulate Decellularized Scaffold

Contact Info

Product

Resources

About

Upcyte^®Microvascular Endothelial Cells Repopulate Decellularized Scaffold