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Regeneration and experimental orthotopic transplantation of a bioengineered kidney

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TLDR
To regenerate functional tissue, rat kidney scaffolds are seeded with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor, resulting in grafts that produced rudimentary urine in vitro when perfused through their intrinsic vascular bed.
Abstract
Approximately 100,000 individuals in the United States currently await kidney transplantation, and 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney's architecture and function and permit perfusion, filtration, secretion, absorption and drainage of urine. We decellularized rat, porcine and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, a collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotopic position in rat, the grafts were perfused by the recipient's circulation and produced urine through the ureteral conduit in vivo.

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Journal ArticleDOI

Engineering kidneys from simple cell suspensions: an exercise in self-organization.

TL;DR: This review describes a technique that begins with a suspension of renogenic stem cells and promotes these cells’ self-organization into organ rudiments very similar to foetal kidneys, with a collecting duct tree, nephrons, corticomedullary zonation and extended loops of Henle.
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Acellular Mouse Kidney ECM can be Used as a Three-Dimensional Substrate to Test the Differentiation Potential of Embryonic Stem Cell Derived Renal Progenitors

TL;DR: It is reported that the extracellular matrix can support the development of kidney structures if the stem cells are first differentiated to kidney progenitor cells before being applied to the acellular organ.
Journal ArticleDOI

Hypertensive rat lungs retain hallmarks of vascular disease upon decellularization but support the growth of mesenchymal stem cells.

TL;DR: The data suggest that diseased hypertensive lungs can be efficiently decellularized similar to control lungs and have the potential to be recellularized with mesenchymal stem cells with the ultimate goal of generating healthy, functional pulmonary tissue.
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Recreating kidney progenitors from pluripotent cells

TL;DR: The understanding of how the embryo goes about specifying the cells of the kidney and the progress to date in adapting this knowledge for the recreation of nephron progenitors and their mature derivatives from pluripotent cells are reviewed.
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Assembly of Human Organs from Stem Cells to Study Liver Disease

TL;DR: This review highlights the most recent advances in organ assembly regarding the development of liver tissue in vitro and discusses applications that involve multiple types of cells with a biomimetic spatial organization for which three-dimensional configurations could be used for drug development or to explain mechanisms of disease.
References
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Journal ArticleDOI

Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart

TL;DR: Eight constructs decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent a cellular valves and intact chamber geometry that could generate pump function in a modified working heart preparation.
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Tissue-engineered autologous bladders for patients needing cystoplasty

TL;DR: Engineered bladder tissues, created with autologous cells seeded on collagen-polyglycolic acid scaffolds, and wrapped in omentum after implantation, can be used in patients who need cystoplasty.
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Regeneration and orthotopic transplantation of a bioartificial lung

TL;DR: Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange, and regenerated lungs into orthotopic position showed in vivo function.
Journal ArticleDOI

HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression

TL;DR: Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen, and it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation.
Journal ArticleDOI

Organ engineering based on decellularized matrix scaffolds

TL;DR: A review summarizes achievements to date and discusses the role of native ECM scaffolds in organ regeneration, which provides a promising alternative to synthetic scaffolds and a foundation for regenerative efforts.
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