Survival and Function of Transplanted Islet Cells on an in Vivo, Vascularized Tissue Engineering Platform in the Rat: A Pilot Study

Brown, David L.; Meagher, Peter; Knight, Kenneth R.; Keramidaris, Effie; Romeo-Meeuw, Rosalind; Penington, Anthony; Morrison, Wayne A.

doi:10.3727/000000006783981909

Cited by 25 publications

(16 citation statements)

References 16 publications

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“…The first is scaffold-based and takes advantage of biological [23,24] or synthetic [25–27] scaffolds. In the scaffold-based strategy, materials and structures determine biological outcomes.…”

Section: Introductionmentioning

confidence: 99%

Effects of silk fibroin fiber incorporation on mechanical properties, endothelial cell colonization and vascularization of PDLLA scaffolds

et al. 2013

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Attainment of functional vascularization of engineered constructs is one of the fundamental challenges of tissue engineering. However, the development of an extracellular matrix in most tissues, including bone, is dependent upon the establishment of a well developed vascular supply. In this study a poly-D,L-lactic acid (PDLLA) salt-leached sponge was modified by incorporation of silk fibroin fibers to create a multicomponent scaffold, in an effort to better support endothelial cell colonization and to promote in vivo vascularization. Scaffolds with and without silk fibroin fibers were compared for microstructure, mechanical properties, ability to maintain cell populations in vitro as well as to permit vascular ingrowth into acellular constructs in vivo. We demonstrated that adding silk fibroin fibers to a PDLLA salt-leached sponge enhanced scaffold properties and heightened its capacity to support endothelial cells in vitro and to promote vascularization in vivo. Therefore refinement of scaffold properties by inclusion of materials with beneficial attributes may promote and shape cellular responses.

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Section: Introductionmentioning

confidence: 99%

Effects of silk fibroin fiber incorporation on mechanical properties, endothelial cell colonization and vascularization of PDLLA scaffolds

et al. 2013

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“…A flow-through model has also been developed in which a silicone tube is longitudinally split to implant artery and vein vessels. Cells targeted to be incorporated into the forming 3D construct (Borschel et al 2006) have been mixed with biodegradeable gels and inserted into the chamber, such that the gel and cell mixture lies adjacent to the implanted vessels within the chamber (Messina et al 2005;Brown et al 2006). We and others have demonstrated survival and certain measures of function for cells mixed with biodegradable gels and implanted within the chambers within small mammals for formation of adipose cells (Messina et al 2005), skeletal muscle cells (Borschel et al 2006;Messina et al 2005) and myocardiac cells (Morritt et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Cardiac cells implanted into a cylindrical, vascularized chamber in vivo: pressure generation and morphology

et al. 2008

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We have previously described a model to implant dissociated cells into a cylindrical, vascularized bed in vivo to promote the formation of functional cardiac muscle constructs. We now investigate the cellular organization and the ability of the constructs to generate intra-luminal pressure. Primary cardiac cells were isolated from hearts of 2-3 day old rats, suspended in fibrin gel and inserted into the lumen of silicone tubing. The silicone tubing was then implanted around the femoral vessels in the groin region of recipient animals. After 3 weeks, the constructs were harvested, placed in an in vitro bath and cannulated via the incorporated femoral artery with a pressure transducer for evaluation of intra-luminal pressure dynamics. Histological evaluation showed the presence of a concentric ring of cardiac cells surrounding the femoral vessels. There was also a significant amount of collagen present around cardiac cells. In addition, we observed a significant amount of neovascularization of the explanted constructs. Electron microscopy showed the presence of longitudinally aligned fibers with a large number of gap junctions. Upon electrical stimulation of a single pulse (7 V, 1.2 ms), the constructs generated an intra-luminal pressure of 1.19 +/- 0.45 mmHg (n = 6). In addition, we were able to electrically pace the constructs at frequencies of 0.5-5 Hz. A Starling behavior of the inverse relation between baseline pressure and twitch pressure was observed. Cardiac cells implanted for 3 weeks into the cylindrical vascularized bed formed a tissue construct that demonstrated many of the contractile properties and morphology expected of functioning cardiac tissues.

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“…Comparable to Tee et al [45,46], they could show the successful transplantation in a rat model, thereby increasing the probability of the translation into clinics in near future. Brown et al [48] worked on the establishment of an axially vascularized pancreatic organoid for therapy of diabetes and as an alternative to challenging transplantations of insulinproducing tissues. They were able to grow functional pancreatic isle tissue within a Matrigel ® matrix.…”

Section: The Av Loop As a Tool To Generate A Multitude Of Different Tmentioning

confidence: 99%

“…Implanted cells remained functional and hormone producing after an implantation time of 3 weeks. Besides using this approach as a possible new treatment option in case of the dysfunction of pancreatic islet cells, it also opens up new ways for studying the transplantation of pancreatic and further tissues [48]. Fiegel et al [49] attempted to generate an organ with similar complexity, the liver, within the AV loop model.…”

Section: The Av Loop As a Tool To Generate A Multitude Of Different Tmentioning

confidence: 99%

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

et al. 2018

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Background: Most of the current treatment options for large-scale tissue defects represent a serious burden for the patients, are often not satisfying, and can be associated with significant side effects. Although major achievements have already been made in the field of tissue engineering, the clinical translation in case of extensive tissue defects is only in its early stages. The main challenge and reason for the failure of most tissue engineering approaches is the missing vascularization within large-scale transplants. Summary: The arteriovenous (AV) loop model is an in vivo tissue engineering strategy for generating axially vascularized tissues using the own body as a bioreactor. A superficial artery and vein are anastomosed to create an AV loop. This AV loop is placed into an implantation chamber for prevascularization of the chamber inside, e.g., a scaffold, cells, and growth factors. Subsequently, the generated tissue can be transplanted with its vascular axis into the defect site and anastomosed to the local vasculature. Since the blood supply of the growing tissue is based on the AV loop, it will be immediately perfused with blood in the recipient site leading to optimal healing conditions even in the case of poorly vascularized defects. Using this tissue engineering approach, a multitude of different axially vascularized tissues could be generated, such as bone, skeletal or heart muscle, or lymphatic tissues. Upscaling from the small animal AV loop model into a preclinical large animal model could pave the way for the first successful attempt in clinical application. Key Messages: The AV loop model is a powerful tool for the generation of different axially vascularized replacement tissues. Due to minimal donor site morbidity and the possibility to generate patient-specific tissues variable in type and size, this in vivo tissue engineering approach can be considered as a promising alternative therapy to current treatment options of large-scale defects.

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Survival and Function of Transplanted Islet Cells on an in Vivo, Vascularized Tissue Engineering Platform in the Rat: A Pilot Study

Cited by 25 publications

References 16 publications

Effects of silk fibroin fiber incorporation on mechanical properties, endothelial cell colonization and vascularization of PDLLA scaffolds

Effects of silk fibroin fiber incorporation on mechanical properties, endothelial cell colonization and vascularization of PDLLA scaffolds

Cardiac cells implanted into a cylindrical, vascularized chamber in vivo: pressure generation and morphology

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

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