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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

      Submit here before July 31, 2024

      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

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      Kidney Regeneration with Stem Cells: An Overview

      Nephron Experimental Nephrology
      S. Karger AG

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          Abstract

          Background: Kidney regeneration is currently gaining considerable attention in place of kidney dialysis as the ultimate therapeutic strategy for renal failure. However, because of anatomical complications, the kidney is believed to be the hardest organ to regenerate. Such a complicated organ is virtually impossible to imagine being completely rebuilt de novo from stem cells. Nevertheless, several research groups are attempting this large challenge. Summary: There are 4 major strategies for de novo kidney regeneration from stem cells. These strategies include the use of: (i) a decellularized cadaveric scaffold, (ii) blastocyst decomplementation, (iii) a nephrogenic niche for growing a xeno-embyro, and (iv) self-assembly potential. All of these strategies may be applicable in the clinical setting, but a substantial preparation period appears to be required. Key Messages: Although many outstanding problems remain for kidney regeneration, including ethical issues and the formation of chimeric structures, trials provide hope for dialysis patients and kidney regeneration is expected to be a reality in the future.

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          Most cited references18

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          Regeneration and orthotopic transplantation of a bioartificial lung.

          About 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with end-stage lung disease. Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange. We decellularized lungs by detergent perfusion and yielded scaffolds with acellular vasculature, airways and alveoli. To regenerate gas exchange tissue, we seeded scaffolds with epithelial and endothelial cells. To establish function, we perfused and ventilated cell-seeded constructs in a bioreactor simulating the physiologic environment of developing lung. By day 5, constructs could be perfused with blood and ventilated using physiologic pressures, and they generated gas exchange comparable to that of isolated native lungs. To show in vivo function, we transplanted regenerated lungs into orthotopic position. After transplantation, constructs were perfused by the recipient's circulation and ventilated by means of the recipient's airway and respiratory muscles, and they provided gas exchange in vivo for up to 6 h after extubation.
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            Regeneration and Experimental Orthotopic Transplantation of a Bioengineered Kidney

            Over 100,000 individuals in the United States currently await kidney transplantation, while 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, collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells, then perfused these cell-seeded constructs in a whole organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused via their intrinsic vascular bed. When transplanted in orthotopic position in rat, the grafts were perfused by the recipient’s circulation, and produced urine via the ureteral conduit in vivo.
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              Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs.

              In the field of regenerative medicine, one of the ultimate goals is to generate functioning organs from pluripotent cells, such as ES cells or induced pluripotent stem cells (PSCs). We have recently generated functional pancreas and kidney from PSCs in pancreatogenesis- or nephrogenesis-disabled mice, providing proof of principle for organogenesis from PSCs in an embryo unable to form a specific organ. Key when applying the principles of in vivo generation to human organs is compensation for an empty developmental niche in large nonrodent mammals. Here, we show that the blastocyst complementation system can be applied in the pig using somatic cell cloning technology. Transgenic approaches permitted generation of porcine somatic cell cloned embryos with an apancreatic phenotype. Complementation of these embryos with allogenic blastomeres then created functioning pancreata in the vacant niches. These results clearly indicate that a missing organ can be generated from exogenous cells when functionally normal pluripotent cells chimerize a cloned dysorganogenetic embryo. The feasibility of blastocyst complementation using cloned porcine embryos allows experimentation toward the in vivo generation of functional organs from xenogenic PSCs in large animals.
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                Author and article information

                Journal
                Nephron Experimental Nephrology
                Nephron Exp Nephrol
                S. Karger AG
                1660-2129
                May 19 2014
                May 1 2014
                May 19 2014
                : 126
                : 2
                : 54-58
                Article
                10.1159/000360662
                6b89ed27-90e8-4b88-8f4e-c467b7a762c6
                © 2014
                History

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