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Gilpin, Sarah

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Gilpin

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Sarah

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Gilpin, Sarah
Author's Publications: search.filters.isAuthorOfPublication.7dcbf961-01ae-4277-b7b8-8ea2bc2664a4

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    Regeneration and Experimental Orthotopic Transplantation of a Bioengineered Kidney
    (2013) Song, Jeremy J; Guyette, Jacques; Gilpin, Sarah; Gonzalez, Gabriel; Vacanti, Joseph; Ott, Harald
    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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    Design and validation of a clinical-scale bioreactor for long-term isolated lung culture
    (2015) Charest, Jonathan M.; Okamoto, Tatsuya; Kitano, Kentaro; Yasuda, Atsushi; Gilpin, Sarah; Mathisen, Douglas; Ott, Harald
    The primary treatment for end-stage lung disease is lung transplantation. However, donor organ shortage remains a major barrier for many patients. In recent years, techniques for maintaining lungs ex vivo for evaluation and short-term (<12h) resuscitation have come into more widespread use in an attempt to expand the donor pool. In parallel, progress in whole organ engineering has provided the potential perspective of patient derived grafts grown on demand. As both of these strategies advance to more complex interventions for lung repair and regeneration, the need for a long-term organ culture system becomes apparent. Herein we describe a novel clinical scale bioreactor capable of maintaining functional porcine and human lungs for at least 72 hours in isolated lung culture (ILC). The fully automated, computer controlled, sterile, closed circuit system enables physiologic pulsatile perfusion and negative pressure ventilation, while gas exchange function, and metabolism can be evaluated. Creation of this stable, biomimetic long-term culture environment will enable advanced interventions in both donor lungs and engineered grafts of human scale.
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    Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts
    (Nature Publishing Group UK, 2017) Kitano, Kentaro; Schwartz, Dana; Zhou, Haiyang; Gilpin, Sarah; Wojtkiewicz, Gregory R.; Ren, Xi; Sommer, Cesar A.; Capilla, Amalia V.; Mathisen, Douglas; Goldstein, Allan; Mostoslavsky, Gustavo; Ott, Harald
    Patients with short bowel syndrome lack sufficient functional intestine to sustain themselves with enteral intake alone. Transplantable vascularized bioengineered intestine could restore nutrient absorption. Here we report the engineering of humanized intestinal grafts by repopulating decellularized rat intestinal matrix with human induced pluripotent stem cell-derived intestinal epithelium and human endothelium. After 28 days of in vitro culture, hiPSC-derived progenitor cells differentiate into a monolayer of polarized intestinal epithelium. Human endothelial cells seeded via native vasculature restore perfusability. Ex vivo isolated perfusion testing confirms transfer of glucose and medium-chain fatty acids from lumen to venous effluent. Four weeks after transplantation to RNU rats, grafts show survival and maturation of regenerated epithelium. Systemic venous sampling and positron emission tomography confirm uptake of glucose and fatty acids in vivo. Bioengineering intestine on vascularized native scaffolds could bridge the gap between cell/tissue-scale regeneration and whole organ-scale technology needed to treat intestinal failure patients.