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      Tissue-Engineered Grafts from Human Decellularized Extracellular Matrices: A Systematic Review and Future Perspectives

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          Abstract

          Tissue engineering and regenerative medicine involve many different artificial and biologic materials, frequently integrated in composite scaffolds, which can be repopulated with various cell types. One of the most promising scaffolds is decellularized allogeneic extracellular matrix (ECM) then recellularized by autologous or stem cells, in order to develop fully personalized clinical approaches. Decellularization protocols have to efficiently remove immunogenic cellular materials, maintaining the nonimmunogenic ECM, which is endowed with specific inductive/differentiating actions due to its architecture and bioactive factors. In the present paper, we review the available literature about the development of grafts from decellularized human tissues/organs. Human tissues may be obtained not only from surgery but also from cadavers, suggesting possible development of Human Tissue BioBanks from body donation programs. Many human tissues/organs have been decellularized for tissue engineering purposes, such as cartilage, bone, skeletal muscle, tendons, adipose tissue, heart, vessels, lung, dental pulp, intestine, liver, pancreas, kidney, gonads, uterus, childbirth products, cornea, and peripheral nerves. In vitro recellularizations have been reported with various cell types and procedures (seeding, injection, and perfusion). Conversely, studies about in vivo behaviour are poorly represented. Actually, the future challenge will be the development of human grafts to be implanted fully restored in all their structural/functional aspects.

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          Most cited references319

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          Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study

          The Lancet, 349(9064), 1498-1504
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            Tissue-engineered lungs for in vivo implantation.

            Because adult lung tissue has limited regeneration capacity, lung transplantation is the primary therapy for severely damaged lungs. To explore whether lung tissue can be regenerated in vitro, we treated lungs from adult rats using a procedure that removes cellular components but leaves behind a scaffold of extracellular matrix that retains the hierarchical branching structures of airways and vasculature. We then used a bioreactor to culture pulmonary epithelium and vascular endothelium on the acellular lung matrix. The seeded epithelium displayed remarkable hierarchical organization within the matrix, and the seeded endothelial cells efficiently repopulated the vascular compartment. In vitro, the mechanical characteristics of the engineered lungs were similar to those of native lung tissue, and when implanted into rats in vivo for short time intervals (45 to 120 minutes) the engineered lungs participated in gas exchange. Although representing only an initial step toward the ultimate goal of generating fully functional lungs in vitro, these results suggest that repopulation of lung matrix is a viable strategy for lung regeneration.
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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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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                18 December 2018
                December 2018
                : 19
                : 12
                : 4117
                Affiliations
                [1 ]Department of Neuroscience, Section of Human Anatomy, University of Padova, Via A. Gabelli 65, 35121 Padova, Italy; andrea.porzionato@ 123456unipd.it (A.P.); silvia.barbon@ 123456yahoo.it (S.B.); veronica.macchi@ 123456unipd.it (V.M.); raffaele.decaro@ 123456unipd.it (R.D.C.)
                [2 ]L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, Via N. Giustiniani 2, 35128 Padova, Italy
                [3 ]Complex Operative Unit—Pediatric Surgery, Hospital of Bolzano, Via L. Bӧhler 5, 39100 Bolzano, Italy; frsncesca.grandi7825@ 123456gmail.com
                Author notes
                [* ]Correspondence: elena.stocco@ 123456gmail.com ; Tel.: +39-049-8272318; Fax: +39-049-8272328
                Article
                ijms-19-04117
                10.3390/ijms19124117
                6321114
                30567407
                a39a1a94-2c9b-4c7d-9a5c-20bdd0bd8262
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 November 2018
                : 12 December 2018
                Categories
                Review

                Molecular biology
                decellularization,human,cell colonization,regenerative medicine,body donation,transplantation,mesenchymal stem cells,extracellular matrix,scaffolds,biomechanics

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