Biological Vascularized Matrix for Bladder Tissue Engineering: Matrix Preparation, Reseeding Technique and Short-Term Implantation in a Porcine Model

Schultheiss, Dirk; Gabouev, Alexander I.; Cebotari, Serghei; Tudorache, I.; Walles, Heike; Schlote, Norbert; Wefer, J.; Kaufmann, Peter; Haverich, Axel; Jonas, Udo; Stief, Christian G.; Mertsching, Heike

doi:10.1097/01.ju.0000145882.80339.18

Cited by 91 publications

(62 citation statements)

References 21 publications

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“…Furthermore, the BioVaSc provides extracellular components, which ensure the adhesion of the cells and facilitate tissue differentiation. It also enables the long-time tissue specific function of bioartificial 3D tissues 7,8,15 . The prerequisite for the engineering of functional vascular substitutes is the mimicking of human physiological and biomechanical conditions.…”

Section: Discussionmentioning

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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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: Discussionmentioning

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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“…120 Scaffold design and construction is another area in which further innovations will be necessary to bring stem cell-based constructs to the clinic. Although EPC-based vascularized scaffolds improve tissue survival after implantation, 121 precise control over oxygen supply will be necessary, both during ex vivo tissue assembly and after implantation, to emulate the mildly hypoxic conditions under which stem cells survive and proliferate. Beyond oxygen supply, the location and concentration of fate-directing molecules must be controlled.…”

Section: Future Directionsmentioning

confidence: 99%

Review:Ex VivoEngineering of Living Tissues with Adult Stem Cells

et al. 2006

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Adult stem cells have the potential to revolutionize regenerative medicine with their unique abilities to self-renew and differentiate into various phenotypes. This review examines progress and challenges in ex vivo tissue engineering with adult stem cells. These rare cells are harvested from a variety of tissues, including bone marrow, adipose, skeletal muscle, and placenta, and differentiate into cells of their own lineage and in some cases atypical lineages. Insight into the stem cell niche leads to the identification of matrix components, soluble factors, and physiological conditions that enhance the ex vivo amplification and differentiation of stem cells. Scaffolds composed of metals, naturally occurring materials, and synthetic polymers organize stem cells into complex spatial groupings that mimic native tissue. Cell signals from covalently bound ligands and slowly released regulatory factors in scaffolds direct stem cell fate. Future advances in stem cell biology and scaffold design will ultimately improve the efficacy of tissue substitutes as implants, in research, and as extracorporeal devices.

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“…[4][5][6] Schultheiss et al repopulated decellularized jejunal segments with endothelial, smooth muscle, and urothelial cells to create a ''prevascularized'' bladder-like tissue; both recellularized and unrecellularized segments were surgically anastomosed to host vessels, with a maximum thrombosis-free perfusion interval of 3 h using a seeded segment. 4 Successful decellularization and recellularization of an intact liver ECM with hepatocytes has also been described. 5 Additionally, Song et al produced engineered rat kidneys via decellularization and repopulation with HUVEC and rat neonatal kidney cells.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 A number of complex tissues and solid organs have been engineered for reconstruction and/or restoration, including skin, trachea, ears, liver, kidney, heart, and lungs. [3][4][5][6][7][8][9] With the exception of cartilage, which is devoid of intrinsic vascularity, all other tissues require an inherent vascular network for survival. As such, virtually any clinical application of human scale-engineered tissues requires a design with an integrated and hierarchical vascular network that may be anastomosed to the host vasculature to preserve the viability of the cellular constituents.…”

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confidence: 99%