Person: Vacanti, Joseph
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Vacanti
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Joseph
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Vacanti, Joseph
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Publication Regeneration and Experimental Orthotopic Transplantation of a Bioengineered Kidney(2013) Song, Jeremy J; Guyette, Jacques; Gilpin, Sarah; Gonzalez, Gabriel; Vacanti, Joseph; Ott, HaraldOver 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.Publication Extensively Expanded Auricular Chondrocytes Form Neocartilage In Vivo(SAGE Publications, 2014) Tseng, Alan; Pomerantseva, Irina; Cronce, Michael J.; Kimura, Anya M.; Neville, Craig; Randolph, Mark; Vacanti, Joseph; Sundback, CathrynObjective: Our goal was to engineer cartilage in vivo using auricular chondrocytes that underwent clinically relevant expansion and using methodologies that could be easily translated into health care practice. Design: Sheep and human chondrocytes were isolated from auricular cartilage biopsies and expanded in vitro. To reverse dedifferentiation, expanded cells were either mixed with cryopreserved P0 chondrocytes at the time of seeding onto porous collagen scaffolds or proliferated with basic fibroblast growth factor (bFGF). After 2-week in vitro incubation, seeded scaffolds were implanted subcutaneously in nude mice for 6 weeks. The neocartilage quality was evaluated histologically; DNA and glycosaminoglycans were quantified. Cell proliferation rates and collagen gene expression profiles were assessed. Results: Clinically sufficient over 500-fold chondrocyte expansion was achieved at passage 3 (P3); cell dedifferentiation was confirmed by the simultaneous COL1A1/3A1 gene upregulation and COL2A1 downregulation. The chondrogenic phenotype of sheep but not human P3 cells was rescued by addition of cryopreserved P0 chondrocytes. With bFGF supplementation, chondrocytes achieved clinically sufficient expansion at P2; COL2A1 expression was not rescued but COL1A1/3A1genes were downregulated. Although bFGF failed to rescue COL2A1 expression during chondrocyte expansion in vitro, elastic neocartilage with obvious collagen II expression was observed on porous collagen scaffolds after implantation in mice for 6 weeks. Conclusions: Both animal and human auricular chondrocytes expanded with low-concentration bFGF supplementation formed high-quality elastic neocartilage on porous collagen scaffolds in vivo.Publication Hepatic tissue engineering: from transplantation to customized cell-based liver directed therapies from the laboratory(Blackwell Publishing Ltd, 2008) Fiegel, Henning C; Kaufmann, Peter M; Bruns, Helge; Kluth, Dietrich; Horch, Raymund E; Vacanti, Joseph; Kneser, UlrichAbstract Today, liver transplantation is still the only curative treatment for liver failure due to end-stage liver diseases. Donor organ shortage, high cost and the need of immunosuppressive medications are still the major limitations in the field of liver transplantation. Thus, alternative innovative cell-based liver directed therapies, for example, liver tissue engineering, are under investigation with the aim that in future an artificial liver tissue could be created and be used for the replacement of the liver function in patients. Using cells instead of organs in this setting should permit (i) expansion of cells in an in vitro phase, (ii) genetic or immunological manipulation of cells for transplantation, (iii) tissue typing and cryopreservation in a cell bank and (iv) the ex vivo genetic modification of patient's own cells prior to re-implantation. Function and differentiation of liver cells are influenced by the three-dimensional organ architecture. The use of polymeric matrices permits the three-dimensional formation of a neo tissue and specific stimulation by adequate modification of the matrix surface, which might be essential for appropriate differentiation of transplanted cells. In addition, culturing hepatocytes on three-dimensional matrices permits culture in a flow bioreactor system with increased function and survival of the cultured cells. Based on bioreactor technology, bioartificial liver devices (BAL) are developed for extracorporeal liver support. Although BALs improved clinical and metabolic conditions, increased patient survival rates have not been proven yet. For intracorporeal liver replacement, a concept that combines tissue engineering using three-dimensional, highly porous matrices with cell transplantation could be useful. In such a concept, whole liver mass transplantation, long-term engraftment and function as well as correction of a metabolic defect in animal models could be achieved with a principally reversible procedure. Future studies have to investigate which environmental conditions and transplantation system would be most suitable for the development of artificial functional liver tissue including blood supply for a potential use in a clinical setting.Publication Consequences of Cold-Ischemia Time on Primary Nonfunction and Patient and Graft Survival in Liver Transplantation: A Meta-Analysis(Public Library of Science, 2008) Stahl, James E.; Kreke, Jennifer E.; Malek, Fawaz Ali Abdul; Schaefer, Andrew J.; Vacanti, JosephIntroduction: The ability to preserve organs prior to transplant is essential to the organ allocation process. Objective: The purpose of this study is to describe the functional relationship between cold-ischemia time (CIT) and primary nonfunction (PNF), patient and graft survival in liver transplant. Methods: To identify relevant articles Medline, EMBASE and the Cochrane database, including the non-English literature identified in these databases, was searched from 1966 to April 2008. Two independent reviewers screened and extracted the data. CIT was analyzed both as a continuous variable and stratified by clinically relevant intervals. Nondichotomous variables were weighted by sample size. Percent variables were weighted by the inverse of the binomial variance. Results: Twenty-six studies met criteria. Functionally, PNF% =26.678281+0.9134701*CIT Mean+0.1250879*(CIT Mean29.89535)^220.0067663*(CIT Mean29.89535)^3, r2 = .625, , p,.0001. Mean patient survival: 93 % (1 month), 88 % (3 months), 83 % (6 months) and 83 % (12 months). Mean graft survival: 85.9 % (1 month), 80.5 % (3 months), 78.1 % (6 months) and 76.8 % (12 months). Maximum patient and graft survival occurred with CITs between 7.5–12.5 hrs at each survival interval. PNF was also significantly correlated with ICU time, % first time grafts and % immunologic mismatches. Conclusion: The results of this work imply that CIT may be the most important pre-transplant information needed in the decision to accept an organ.