A Whole-Organ Regenerative Medicine Approach for Liver Replacement
Open accessAbstract
BACKGROUND & AIMS: The therapy of choice for end-stage liver disease is whole-organ liver transplantation, but this option is limited by a shortage of donor organs. Cell-based therapies and hepatic tissue engineering have been considered as alternatives to liver transplantation, but neither has proven effective to date. A regenerative medicine approach for liver replacement has recently been described that includes the use of a three-dimensional organ scaffold prepared by decellularization of xenogeneic liver. The present study investigates a new, minimally disruptive method for whole-organ liver decellularization and three different cell reseeding strategies to engineer functional liver tissue. METHODS: A combination of enzymatic, detergent, and mechanical methods are used to remove all cells from isolated rat livers. Whole-organ perfusion is used in a customized organ chamber and the decellularized livers are examined by morphologic, biochemical, and immunolabeling techniques for preservation of the native matrix architecture and composition. Three different methods for hepatocyte seeding of the resultant three-dimensional liver scaffolds are evaluated to maximize cell survival and function: (1) direct parenchymal injection, (2) multistep infusion, or (3) continuous perfusion. RESULTS: The decellularization process preserves the three-dimensional macrostructure, the ultrastructure, the composition of the extracellular matrix components, the native microvascular network of the liver, and the bile drainage system, and up to 50% of growth factor content. The three-dimensional liver matrix reseeded with the multistep infusion of hepatocytes generated ∼90% of cell engraftment and supported liver-specific functional capacities of the engrafted cells, including albumin production, urea metabolism, and cytochrome P450 induction. CONCLUSIONS: Whole-organ liver decellularization is possible with maintenance of structure and composition suitable to support functional hepatocytes.
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Enzymatic treatment, particularly involving nucleases and trypsin, is often combined with chemical detergents followed by various washing cycles for liver decellularization.
“Hence, enzymatic treatment, particularly involving nucleases and trypsin, is often combined with chemical detergents followed by various washing cycles for liver decellularization [110,123,149,150].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [110]
The biliary tree is maintained post-perfusion decellularization, requiring only reseeding by cholangiocytes to restore functionality.
“Furthermore, the biliary tree is maintained post-perfusion decellularization, requiring only reseeding by cholangiocytes to restore functionality [110].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [110]
Primary murine hepatocytes have demonstrated the ability to attach, grow, proliferate, and survive within decellularized rodent livers while retaining their morphology and function.
“Primary murine hepatocytes are frequently used for recellularization experiments and have demonstrated the ability to attach, grow, proliferate, and survive within decellularized rodent livers while retaining their morphology and function [12,110,203].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [110]
Soto-Gutierrez et al. demonstrated that a multistep infusion of cells via the portal vein resulted in a better parenchymal repopulation rate, with a cell engraftment rate of approximately 90%, and exhibited higher proliferative capacity as well as a superior functional profile of engrafted cells, including albumin production, CYP1A1/2 activity, and ammonia clearance, compared to direct parenchymal
“For example, Soto-Gutierrez et al. demonstrated that a multistep infusion of cells via the portal vein resulted in a better parenchymal repopulation rate, with a cell engraftment rate of approximately 90 %, and exhibited higher proliferative capacity as well as a superior functional profile of engrafted cells, including albumin production, CYP1A1/2 activity, and ammonia clearance, compared to”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [110]
The biliary network tree is confirmed to be intact after decellularization by scan electron microscopy, corrosion cast, dye perfusion, and contrast radiography; only reconstruction by bile duct cells is necessary.
“Fortunately, the biliary network tree is confirmed to be intact after decellularization by scan electron microscopy, corrosion cast, dye perfusion, and contrast radiography; only reconstruction by bile duct cells is necessary [12,110,170,198].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [110]
Cites
An overview of tissue and whole organ decellularization processes
Crapo, P. M., Gilbert, T. W., & Badylak, S. F. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.01.057 · Cited by 3,591 · see citing works
Self-citationPerfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart
Ott, H. C., Matthiesen, T. S., Goh, S.-K., Black, L. D., Kren, S. M., Netoff, T. I., & Taylor, D. A. (2008) · Nature Medicine · doi:10.1038/nm1684 · Cited by 2,650 · see citing works
Extracellular matrix as a biological scaffold material: Structure and function
BADYLAK, S., FREYTES, D., & GILBERT, T. (2009) · Acta Biomaterialia · doi:10.1016/j.actbio.2008.09.013 · Cited by 1,671 · see citing works
Self-citationUygun, B. E., Soto-Gutierrez, A., Yagi, H., Izamis, M.-L., Guzzardi, M. A., Shulman, C., Milwid, J., Kobayashi, N., Tilles, A., Berthiaume, F., et al. (2010) · Nature Medicine · doi:10.1038/nm.2170 · Cited by 1,370 · see citing works
Reprint of: Extracellular matrix as a biological scaffold material: Structure and function
Badylak, S. F., Freytes, D. O., & Gilbert, T. W. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.07.016 · Cited by 1,361 · see citing works
Self-citationTissue-Engineered Lungs for in Vivo Implantation
Petersen, T. H., Calle, E. A., Zhao, L., Lee, E. J., Gui, L., Raredon, M. S. B., Gavrilov, K., Yi, T., Zhuang, Z. W., Breuer, C. K., et al. (2010) · Science · doi:10.1126/science.1189345 · Cited by 1,177 · see citing works
Regeneration and orthotopic transplantation of a bioartificial lung
Ott, H. C., Clippinger, B., Conrad, C., Schuetz, C., Pomerantseva, I., Ikonomou, L., Kotton, D., & Vacanti, J. P. (2010) · Nature Medicine · doi:10.1038/nm.2193 · Cited by 1,090 · see citing works
Organ Donation and Utilization in the United States, 1996–2005
Punch, J. D., Hayes, D. H., LaPorte, F. B., McBride, V., & Seely, M. S. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.01779.x · Cited by 600 · see citing works
Basal lamina scaffold-anatomy and significance for maintenance of orderly tissue structure.
Vracko, R. (1974) · PubMed Central · Cited by 551 · see citing works
Differentiation and Transplantation of Human Embryonic Stem Cell–Derived Hepatocytes
Basma, H., Soto–Gutiérrez, A., Yannam, G. R., Liu, L., Ito, R., Yamamoto, T., Ellis, E. C. S., Carson, S. D., Sato, S., Chen, Y., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.10.047 · Cited by 509 · see citing works
Self-citationQuantification of DNA in Biologic Scaffold Materials
Gilbert, T. W., Freund, J. M., & Badylak, S. F. (2008) · Journal of Surgical Research · doi:10.1016/j.jss.2008.02.013 · Cited by 482 · see citing works
Self-citationCortiella, J., Niles, J. A., Cantu, A., Brettler, A. C., Pham, A. N., Vargas, G., Winston, S., Wang, J. P., Walls, S., & Nichols, J. E. (2010) · Tissue Engineering Part A · doi:10.1089/ten.tea.2009.0730 · Cited by 381 · see citing works
Preparation of Cardiac Extracellular Matrix from an Intact Porcine Heart
Wainwright, J. M., Czajka, C. A., Patel, U. B., Freytes, D. O., Tobita, K., Gilbert, T. W., & Badylak, S. F. (2009) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2009.0392 · Cited by 327 · see citing works
Self-citationTilles, A. W., Baskaran, H., Roy, P., Yarmush, M. L., & Toner, M. (2001) · Biotechnology and Bioengineering · doi:10.1002/bit.1071 · Cited by 326 · see citing works
Maintenance of Human Hepatocyte Function In Vitro by Liver-Derived Extracellular Matrix Gels
Sellaro, T. L., Ranade, A. R., Faulk, D. M., McCabe, G. P., Dorko, K., Badylak, S. F., & Strom, S. C. (2009) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0587 · Cited by 276 · see citing works
Self-citationOrgan Donation and Utilization in the United States, 1999-2008
Klein, A. S., Messersmith, E. E., Ratner, L. E., Kochik, R. A., Baliga, P. K., & OJO, A. O. (2010) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2009.03008.x · Cited by 272 · see citing works
Soto–Gutiérrez, A., Kobayashi, N., Rivas‐Carrillo, J. D., Navarro–Álvarez, N., Zhao, D., Okitsu, T., Noguchi, H., Basma, H., Tabata, Y., Chen, Y., et al. (2006) · Nature Biotechnology · doi:10.1038/nbt1257 · Cited by 219 · see citing works
Self-citationSellaro, T. L., Ravindra, A. K., Stolz, D. B., & Badylak, S. F. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0437 · Cited by 214 · see citing works
Self-citationKidambi, S., Yarmush, R. S., Novik, E., Chao, P., Yarmush, M. L., & Nahmias, Y. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906820106 · Cited by 213 · see citing works
Method for the decellularization of intact rat liver
Shupe, T. D., Williams, M. J., Brown, A. R., Willenberg, B., & Petersen, B. E. (2010) · Organogenesis · doi:10.4161/org.6.2.11546 · Cited by 175 · see citing works
Epimorphic regeneration approach to tissue replacement in adult mammals
Agrawal, V., Johnson, S. A., Reing, J. E., Zhang, L., Tottey, S., Wang, G., Hirschi, K. K., Braunhut, S. J., Gudas, L. J., & Badylak, S. F. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905851106 · Cited by 160 · see citing works
Self-citationBarriers to the successful treatment of liver disease by hepatocyte transplantation
Soltys, K. A., Soto–Gutiérrez, A., Nagaya, M., Baskin, K. M., Deutsch, M., Ito, R., Shneider, B. L., Squires, R. H., Vockley, J. E., Guha, C., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.05.010 · Cited by 143 · see citing works
Self-citationStraub, A. C., Clark, K. A. A., Ross, M. A., Chandra, A. G., Li, S., Gao, X., Pagano, P. J., Stolz, D. B., & Barchowsky, A. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35092 · Cited by 121 · see citing works
Self-citationTruncated Thioredoxin: Physiological Functions and Mechanism
Pekkari, K., & Holmgren, A. (2004) · Antioxidants and Redox Signaling · doi:10.1089/152308604771978345 · Cited by 111 · see citing works
Assessment of Artificial Liver Support Technology
Yarmush, M. L., Dunn, J., & Tompkins, R. G. (1992) · Cell Transplantation · doi:10.1177/096368979200100501 · Cited by 100 · see citing works
Cell Delivery: From Cell Transplantation to Organ Engineering
Soto-Gutierrez, A., Yagi, H., Uygun, B., Navarro-Alvarez, N., Uygun, K., Kobayashi, N., Yang, Y.-G., & Yarmush, M. (2010) · Cell Transplantation · doi:10.3727/096368910x508753 · Cited by 64 · see citing works
Stamatoglou, S. C., Enrich, C., Manson, M. M., & Hughes, R. C. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.116.6.1507 · Cited by 62 · see citing works
Engineering of an Hepatic Organoid to Develop Liver Assist Devices
Soto–Gutiérrez, A., Navarro–Álvarez, N., Yagi, H., Nahmias, Y., Yarmush, M. L., & Kobayashi, N. (2010) · Cell Transplantation · doi:10.3727/096368910x508933 · Cited by 51 · see citing works
Effects of Bergamottin on Human and Monkey Drug-Metabolizing Enzymes in Primary Cultured Hepatocytes
Wen, Y. H., Sahi, J., Urda, E. R., Kulkarni, S., Rose, K., Zheng, X., Sinclair, J. F., Cai, H., Strom, S. C., & Kostrubsky, V. E. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.9.977 · Cited by 48 · see citing works
Self-citationNavarro–Álvarez, N., Soto–Gutiérrez, A., Chen, Y., Caballero-Corbalán, J., Hassan, W. A. R. A., Kobayashi, S., Kondo, Y., Iwamuro, M., Yamamoto, K., Kondo, E., et al. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.11.019 · Cited by 39 · see citing works
Self-citationTorii, T., Miyazawa, M., & Koyama, I. (2005) · Transplantation Proceedings · doi:10.1016/j.transproceed.2005.10.118 · Cited by 24 · see citing works
Soto–Gutiérrez, A., Navarro–Álvarez, N., Rivas‐Carrillo, J. D., Tanaka, K., Chen, Y., Misawa, H., Okitsu, T., Noguchi, H., Tanaka, N., & Kobayashi, N. (2007) · Transplantation · doi:10.1097/01.tp.0000250561.14108.03 · Cited by 23 · see citing works
Flagged first, then by citations
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Decellularization Strategies for Regenerative Medicine: From Processing Techniques to Applications
Gilpin, A., & Yang, Y. (2017) · BioMed Research International · doi:10.1155/2017/9831534 · Cited by 742 · see citing works
Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance
Keane, T. J., Swinehart, I. T., & Badylak, S. F. (2015) · Methods · doi:10.1016/j.ymeth.2015.03.005 · Cited by 670 · see citing works
Self-citationDecellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation
Mazza, G., Rombouts, K., Rennie Hall, A., Urbani, L., Vinh Luong, T., Al-Akkad, W., Longato, L., Brown, D., Maghsoudlou, P., Dhillon, A. P., et al. (2015) · Scientific Reports · doi:10.1038/srep13079 · Cited by 415 · see citing works
RETRACTED: Engineered whole organs and complex tissues
Badylak, S. F., Weiss, D. J., Caplan, A., & Macchiarini, P. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60073-7 · Cited by 417 · see citing works
Self-citationRetractedSullivan, D. C., Mirmalek-Sani, S.-H., Deegan, D. B., Baptista, P. M., Aboushwareb, T., Atala, A., & Yoo, J. J. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.07.023 · Cited by 363 · see citing works
Decellularized matrices in regenerative medicine
Taylor, D. A., Sampaio, L. C., Ferdous, Z., Gobin, A. S., & Taite, L. J. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.04.044 · Cited by 339 · see citing works
Cell and tissue engineering for liver disease
Bhatia, S. N., Underhill, G. H., Zaret, K. S., & Fox, I. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3005975 · Cited by 309 · see citing works
Self-citationGoh, S.-K., Bertera, S., Olsen, P., Candiello, J., Halfter, W. M., Uechi, G. T., Balasubramani, M., Johnson, S. A., Sicari, B. M., Kollar, E. W., et al. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.05.066 · Cited by 272 · see citing works
Self-citationParmaksiz, M., Dogan, A., Odabas, S., Elçin, A. E., & Elçin, Y. M. (2016) · Biomedical Materials · doi:10.1088/1748-6041/11/2/022003 · Cited by 268 · see citing works
Strategies for tissue and organ decellularization
Gilbert, T. W. (2012) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24130 · Cited by 267 · see citing works
Tissue engineering by decellularization and 3D bioprinting
Garreta, E., Oria, R., Tarantino, C., Pla‐Roca, M., Prado, P., Fernández‐Avilés, F., Campistol, J. M., Samitier, J., & Montserrat, N. (2017) · Materials Today · doi:10.1016/j.mattod.2016.12.005 · Cited by 263 · see citing works
Biologic scaffold composed of skeletal muscle extracellular matrix
Wolf, M. T., Daly, K. A., Reing, J. E., & Badylak, S. F. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2011.12.055 · Cited by 259 · see citing works
Self-citationBiocompatibility of Subcutaneously Implanted Plant-Derived Cellulose Biomaterials
Modulevsky, D. J., Cuerrier, C. M., & Pelling, A. E. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157894 · Cited by 254 · see citing works
Rana, D., Zreiqat, H., Benkirane-Jessel, N., Ramakrishna, S., & Ramalingam, M. (2017) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2061 · Cited by 243 · see citing works
Lee, J. S., Shin, J., Park, H.-M., Kim, Y.-G., Kim, B.-G., Oh, J.-W., & Cho, S.-W. (2014) · Biomacromolecules · doi:10.1021/bm4015039 · Cited by 236 · see citing works
A review of cellularization strategies for tissue engineering of whole organs
Scarritt, M. E. (2015) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2015.00043 · Cited by 234 · see citing works
Biologic Scaffolds for Regenerative Medicine: Mechanisms of In vivo Remodeling
Londoño, R., & Badylak, S. F. (2014) · Annals of Biomedical Engineering · doi:10.1007/s10439-014-1103-8 · Cited by 232 · see citing works
Self-citationOrlando, G., Farney, A. C., Iskandar, S. S., Mirmalek-Sani, S.-H., Sullivan, D. C., Moran, E., AbouShwareb, T., De Coppi, P., Wood, K. J., Stratta, R. J., et al. (2012) · Annals of Surgery · doi:10.1097/sla.0b013e31825a02ab · Cited by 229 · see citing works
Caralt, M., Uzarski, J. S., Iacob, S., Obergfell, K. P., Berg, N., Bijonowski, B. M., Kiefer, K. M., Ward, H. H., Wandinger‐Ness, A., Miller, W. M., et al. (2014) · American Journal of Transplantation · doi:10.1111/ajt.12999 · Cited by 220 · see citing works
The effect of detergents on the basement membrane complex of a biologic scaffold material
Faulk, D. M., Carruthers, C. A., Warner, H. J., Kramer, C. R., Reing, J. E., Zhang, L., D’Amore, A., & Badylak, S. F. (2013) · Acta Biomaterialia · doi:10.1016/j.actbio.2013.09.006 · Cited by 220 · see citing works
Self-citationBiocompatibility evaluation of tissue-engineered decellularized scaffolds for biomedical application
Hussein, K. H., Park, K.-M., Kang, K.-S., & Woo, H.-M. (2016) · Materials Science and Engineering: C · doi:10.1016/j.msec.2016.05.068 · Cited by 218 · see citing works
Kim, B. S., Kim, H., Gao, G., Jang, J., & Cho, D. (2017) · Biofabrication · doi:10.1088/1758-5090/aa7e98 · Cited by 207 · see citing works
Yoon No, D., Lee, K.-H., Lee, J., & Lee, S.-H. (2015) · Lab on a Chip · doi:10.1039/c5lc00611b · Cited by 205 · see citing works
Human-Scale Whole-Organ Bioengineering for Liver Transplantation: A Regenerative Medicine Approach
Yagi, H., Fukumitsu, K., Fukuda, K., Kitago, M., Shinoda, M., Obara, H., Itano, O., Kawachi, S., Tanabe, M., Coudriet, G. M., et al. (2013) · Cell Transplantation · doi:10.3727/096368912x654939 · Cited by 188 · see citing works
Self-citationStem Cells and Regenerative Medicine: Myth or Reality of the 21th Century
Stoltz, J., de Isla, N., Li, Y., Bensoussan, D., Zhang, L., Huselstein, C., Chen, Y., Decot, V., Magdalou, J., Li, N., et al. (2015) · Stem Cells International · doi:10.1155/2015/734731 · Cited by 152 · see citing works
Self-citationLiver support strategies: cutting-edge technologies
Struecker, B., Raschzok, N., & Sauer, I. M. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.204 · Cited by 165 · see citing works
He, M., & Callanan, A. (2012) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2012.0340 · Cited by 160 · see citing works
Decellularization and Recellularization Technologies in Tissue Engineering
Fu, R., Wang, Y.-C., Liu, S., Shih, T.-R., Lin, H.-L., Chen, Y.-M., Sung, J.-H., Lu, C.-H., Wei, J.-R., Wang, Z.-W., et al. (2014) · Cell Transplantation · doi:10.3727/096368914x678382 · Cited by 158 · see citing works
3D in vitro models of liver fibrosis
van Grunsven, L. A. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.07.004 · Cited by 154 · see citing works
Hwang, J., San, B. H., Turner, N. J., White, L. J., Faulk, D. M., Badylak, S. F., Li, Y., & Yu, S. M. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.01.079 · Cited by 152 · see citing works
Self-citationDecellularized extracellular matrix mediates tissue construction and regeneration
Liu, C., Pei, M., Li, Q., & Zhang, Y. (2021) · Frontiers of Medicine · doi:10.1007/s11684-021-0900-3 · Cited by 146 · see citing works
Zhang, J., Hu, Z. Q., Turner, N. J., Teng, S. F., Cheng, W. Y., Zhou, H. Y., Zhang, L., Hu, H. W., Wang, Q., & Badylak, S. F. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.02.040 · Cited by 141 · see citing works
Self-citationLarge‐Scale Production of LGR5‐Positive Bipotential Human Liver Stem Cells
Schneeberger, K., Sánchez‐Romero, N., Ye, S., van Steenbeek, F. G., Oosterhoff, L. A., Pla Palacin, I., Chen, C., van Wolferen, M. E., van Tienderen, G., Lieshout, R., et al. (2020) · Hepatology · doi:10.1002/hep.31037 · Cited by 141 · see citing works
Costa, A., Naranjo, J. D., Londono, R., & Badylak, S. F. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025676 · Cited by 135 · see citing works
Self-citation"Tissue Papers" from organ-specific decellularized extracellular matrices
Jakus, A. E., Laronda, M. M., Rashedi, A. S., Robinson, C. M., Lee, C., Jordan, S. W., Orwig, K. E., Woodruff, T. K., & Shah, R. N. (2017) · Advanced Functional Materials · doi:10.1002/adfm.201700992 · Cited by 133 · see citing works
Liver tissue engineering: From implantable tissue to whole organ engineering
Mazza, G., Al‐Akkad, W., Rombouts, K., & Pinzani, M. (2017) · Hepatology Communications · doi:10.1002/hep4.1136 · Cited by 127 · see citing works
Role of the Extracellular Matrix in Whole Organ Engineering
Faulk, D. M., Johnson, S. A., Zhang, L., & Badylak, S. F. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24532 · Cited by 127 · see citing works
Self-citationRen, H., Shi, X., Tao, L., Xiao, J., Han, B., Zhang, Y., Yuan, X., & Ding, Y. (2013) · Liver International · doi:10.1111/liv.12088 · Cited by 127 · see citing works
Nicolas, C. T., Hickey, R., Chen, H. S., Mao, S., Higuita, M. L., Wang, Y.-J., & Nyberg, S. (2016) · Stem Cells · doi:10.1002/stem.2500 · Cited by 111 · see citing works
Laurent, J., Blin, G., Chatelain, F., Vanneaux, V., Fuchs, A., Larghero, J., & Théry, M. (2017) · Nature Biomedical Engineering · doi:10.1038/s41551-017-0166-x · Cited by 117 · see citing works
Takeishi, K., Collin de l’Hortet, A., Wang, Y., Handa, K., Guzman-Lepe, J., Matsubara, K., Morita, K., Jang, S., Haep, N., Florentino, R. M., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107711 · Cited by 118 · see citing works
Self-citationJiang, W.-C., Cheng, Y.-H., Yen, M.-H., Chang, Y., Yang, V. W., & Lee, O. K. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.01.024 · Cited by 117 · see citing works
Immunogenicity of Decellularized Porcine Liver for Bioengineered Hepatic Tissue
Mirmalek-Sani, S.-H., Sullivan, D. C., Zimmerman, C., Shupe, T. D., & Petersen, B. E. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.05.002 · Cited by 115 · see citing works
Perspectives on whole-organ assembly: moving toward transplantation on demand
Soto–Gutiérrez, A., Wertheim, J. A., Ott, H. C., & Gilbert, T. W. (2012) · Journal of Clinical Investigation · doi:10.1172/jci61974 · Cited by 115 · see citing works
Wang, B., Jakus, A. E., Baptista, P. M., Söker, S., Soto–Gutiérrez, A., Abecassis, M. M., Shah, R. N., & Wertheim, J. A. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0235 · Cited by 114 · see citing works
Park, Y., Huh, K. M., & Kang, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052491 · Cited by 115 · see citing works
Decellularized scaffolds in regenerative medicine
Yu, Y., Alkhawaji, A., Ding, Y., & Mei, J. (2016) · Oncotarget · doi:10.18632/oncotarget.10945 · Cited by 113 · see citing works
Cellular Mechanisms of Liver Regeneration and Cell-Based Therapies of Liver Diseases
Kholodenko, I. V., & Yarygin, K. N. (2017) · BioMed Research International · doi:10.1155/2017/8910821 · Cited by 113 · see citing works
Regenerative Medicine as Applied to General Surgery
Orlando, G., Wood, K. J., Coppi, P. D., Baptista, P. M., Binder, K. W., Bitar, K. N., Breuer, C. K., Burnett, L., Christ, G. J., Farney, A. C., et al. (2012) · Annals of Surgery · doi:10.1097/sla.0b013e318243a4db · Cited by 112 · see citing works
Tissue Engineering in Liver Regenerative Medicine: Insights into Novel Translational Technologies
Heydari, Z., Najimi, M., Mirzaei, H., Shpichka, A. I., Ruoß, M., Farzaneh, Z., Montazeri, L., Piryaei, A., Timashev, P. S., Gramignoli, R., et al. (2020) · Cells · doi:10.3390/cells9020304 · Cited by 111 · see citing works
Self-citationFaulk, D. M., Wildemann, J. D., & Badylak, S. F. (2015) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2014.03.043 · Cited by 108 · see citing works
Self-citationBiotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells
Chen, C., Soto–Gutiérrez, A., Baptista, P. M., & Spee, B. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.01.066 · Cited by 103 · see citing works
de l’Hortet, A. C., Takeishi, K., Guzman‐Lepe, J., Morita, K., Achreja, A., Popovic, B., Wang, Y., Handa, K., Mittal, A., Meurs, N., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.017 · Cited by 101 · see citing works
Self-citationMachine perfusion of the liver and bioengineering
Schlegel, A. A., Mergental, H., Fondevila, C., Porte, R. J., Friend, P. J., & Dutkowski, P. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.02.009 · Cited by 99 · see citing works
T‐cell‐mediated immunological barriers to xenotransplantation
Scalea, J. R., Hanecamp, I., Robson, S. C., & Yamada, K. (2012) · Xenotransplantation · doi:10.1111/j.1399-3089.2011.00687.x · Cited by 95 · see citing works
Heterogeneity of Scaffold Biomaterials in Tissue Engineering
Edgar, L., McNamara, K., Wong, T., Tamburrini, R., Katari, R., & Orlando, G. (2016) · Materials · doi:10.3390/ma9050332 · Cited by 96 · see citing works
Tang, Z., & Okano, T. (2014) · Regenerative Biomaterials · doi:10.1093/rb/rbu011 · Cited by 89 · see citing works
Maghsoudlou, P., Georgiades, F., Smith, H., Milan, À., Shangaris, P., Urbani, L., Loukogeorgakis, S., Lombardi, B., Mazza, G., Hagen, C. K., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0155324 · Cited by 90 · see citing works
Induced Pluripotent Stem Cell–Derived Endothelial Cells
Jang, S. K., de l’Hortet, A. C., & Soto–Gutiérrez, A. (2019) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.12.004 · Cited by 85 · see citing works
Devalliere, J., Chen, Y., Dooley, K., Yarmush, M. L., & Uygun, B. E. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.07.046 · Cited by 84 · see citing works
He, M., Callanan, A., Lagaras, K., Steele, J. A. M., & Stevens, M. M. (2016) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.33668 · Cited by 81 · see citing works
Lee, S. Y., Kim, H., & Choi, D. (2015) · International Journal of Stem Cells · doi:10.15283/ijsc.2015.8.1.36 · Cited by 80 · see citing works
Pellegata, A. F., Asnaghi, M. A., Stefani, I., Maestroni, A., Maestroni, S., Dominioni, T., Zonta, S., Zerbini, G., & Mantero, S. (2013) · BioMed Research International · doi:10.1155/2013/918753 · Cited by 79 · see citing works
The impact of decellularization agents on renal tissue extracellular matrix
Poornejad, N., Schaumann, L. B., Buckmiller, E. M., Momtahan, N., Gassman, J. R., Ma, H. H., Roeder, B. L., Reynolds, P. R., & Cook, A. D. (2016) · Journal of Biomaterials Applications · doi:10.1177/0885328216656099 · Cited by 78 · see citing works
Application of whole-organ tissue engineering in hepatology
Uygun, B. E., Yarmush, M. L., & Uygun, K. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.140 · Cited by 76 · see citing works
Solubilized liver extracellular matrix maintains primary rat hepatocyte phenotype <i>in‐vitro</i>
Loneker, A. E., Faulk, D. M., Hussey, G. S., D'Amore, A., & Badylak, S. F. (2016) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.35636 · Cited by 75 · see citing works
Self-citationShaheen, M. F., Joo, D. J., Ross, J. J., Anderson, B. D., Chen, H. S., Huebert, R. C., Li, Y., Amiot, B., Young, A., Zlochiver, V., et al. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0460-x · Cited by 75 · see citing works
Struecker, B., Hillebrandt, K. H., Voitl, R., Butter, A., Schmuck, R. B., Reutzel‐Selke, A., Geisel, D., Joehrens, K., Pickerodt, P. A., Raschzok, N., et al. (2014) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2014.0321 · Cited by 74 · see citing works
Biomaterials to Prevascularize Engineered Tissues
Tian, L., & George, S. C. (2011) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-011-9301-3 · Cited by 72 · see citing works
Zhou, Q., Li, L., & Li, . (2014) · Liver International · doi:10.1111/liv.12581 · Cited by 71 · see citing works
Lascaris, B., de Meijer, V. E., & Porte, R. J. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.04.033 · Cited by 69 · see citing works
Hussein, K. H., Saleh, T., Ahmed, E., Kwak, H., Park, K., Yang, S., Kang, B., Choi, K., Kang, K., & Woo, H. (2018) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.36407 · Cited by 67 · see citing works
Wu, Q., Bao, J., Zhou, Y., Wang, Y., Du, Z., Shi, Y., Li, L., & Bu, H. (2015) · BioMed Research International · doi:10.1155/2015/785474 · Cited by 66 · see citing works
Struecker, B., Butter, A., Hillebrandt, K., Polenz, D., Reutzel-Selke, A., Tang, P., Lippert, S., Leder, A., Rohn, S., Geisel, D., et al. (2017) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.1948 · Cited by 65 · see citing works
Human Induced Pluripotent Stem Cells in Hepatology
Gerbal‐Chaloin, S., Funakoshi, N., Caillaud, A., Gondeau, C., Champon, B., & Si‐Tayeb, K. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.09.026 · Cited by 64 · see citing works
Bioengineering Organs for Blood Detoxification
Legallais, C., Kim, D., Mihaila, S. M., Mihajlovic, M., Figliuzzi, M., Bonandrini, B., Salerno, S., Yengej, F. A. Y., Rookmaaker, M. B., Romero, N. S., et al. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201800430 · Cited by 62 · see citing works
Kojima, H., Yasuchika, K., Fukumitsu, K., Ishii, T., Ogiso, S., Miyauchi, Y., Yamaoka, R., Kawai, T., Katayama, H., Yoshitoshi-Uebayashi, E. Y., et al. (2018) · American Journal of Transplantation · doi:10.1111/ajt.14666 · Cited by 60 · see citing works
Self-citationOgiso, S., Yasuchika, K., Fukumitsu, K., Ishii, T., Kojima, H., Miyauchi, Y., Yamaoka, R., Komori, J., Katayama, H., Kawai, T., et al. (2016) · Scientific Reports · doi:10.1038/srep35887 · Cited by 59 · see citing works
Self-citationMesenchymal stem cells support hepatocyte function in engineered liver grafts
Kadota, Y., Yagi, H., Inomata, K., Matsubara, K., Hibi, T., Abe, Y., Kitago, M., Shinoda, M., Obara, H., Itano, O., et al. (2014) · Organogenesis · doi:10.4161/org.27879 · Cited by 58 · see citing works
Krishtul, S., Baruch, L., & Machluf, M. (2019) · Advanced Functional Materials · doi:10.1002/adfm.201900386 · Cited by 58 · see citing works
Recent advances in liver engineering with decellularized scaffold
Dai, Q., Jiang, W., Huang, F., Song, F., Zhang, J., & Zhao, H. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.831477 · Cited by 57 · see citing works
A Hepatic Scaffold from Decellularized Liver Tissue: Food for Thought
Croce, S., Peloso, A., Zoro, T., Avanzini, M. A., & Cobianchi, L. (2019) · Biomolecules · doi:10.3390/biom9120813 · Cited by 58 · see citing works
Hepatocyte Transplantation: Cell Sheet Technology for Liver Cell Transplantation
Tatsumi, K., & Okano, T. (2017) · Current Transplantation Reports · doi:10.1007/s40472-017-0156-7 · Cited by 57 · see citing works
Decellularized liver as a translucent ex vivo model for vascular embolization evaluation
Gao, Y., Li, Z., Hong, Y., Li, T., Hu, X., Sun, L., Chen, Z., Chen, Z., Luo, Z., Wang, X., et al. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.119855 · Cited by 57 · see citing works
Whole Organ Engineering: Approaches, Challenges, and Future Directions
Sohn, S., Buskirk, M. V., Buckenmeyer, M. J., Londoño, R., & Faulk, D. M. (2020) · Applied Sciences · doi:10.3390/app10124277 · Cited by 55 · see citing works
Self-citationFreezing/Thawing without Cryoprotectant Damages Native but not Decellularized Porcine Renal Tissue
Poornejad, N., Frost, T. S., Scott, D. R., Elton, B. B., Reynolds, P. R., Roeder, B. L., & Cook, A. D. (2015) · Organogenesis · doi:10.1080/15476278.2015.1022009 · Cited by 54 · see citing works
Bioengineering in Organ Transplantation: Targeting the Liver
Fukumitsu, K., Yagi, H., & Soto–Gutiérrez, A. (2011) · Transplantation Proceedings · doi:10.1016/j.transproceed.2011.05.014 · Cited by 54 · see citing works
Self-citationZhang, J., Chan, H. F., Wang, H., Shao, D., Tao, Y., & Li, M. (2021) · Journal of Tissue Engineering · doi:10.1177/2041731420986711 · Cited by 54 · see citing works
Use of Myocardial Matrix in a Chitosan-Based Full-Thickness Heart Patch
Pok, S., Benavides, O. M., Hallal, P., & Jacot, J. G. (2014) · Tissue Engineering Part A · doi:10.1089/ten.tea.2013.0620 · Cited by 53 · see citing works
Controlled processing of a full-sized porcine liver to a decellularized matrix in 24 h
Bühler, N. E. M., Schulze-Osthoff, K., Königsrainer, A., & Schenk, M. (2015) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2014.10.019 · Cited by 51 · see citing works
Jiang, B., Suen, R. M., Wertheim, J. A., & Ameer, G. A. (2016) · Biomacromolecules · doi:10.1021/acs.biomac.6b01330 · Cited by 52 · see citing works
Uzarski, J. S., Bijonowski, B. M., Wang, B., Ward, H. H., Wandinger‐Ness, A., Miller, W. M., & Wertheim, J. A. (2015) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2014.0665 · Cited by 49 · see citing works
Will Regenerative Medicine Replace Transplantation?Preprint
Orlando, G., Söker, S., Stratta, R. J., & Atala, A. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a015693 · Cited by 49 · see citing works
Decellularization Strategies for Regenerating Cardiac and Skeletal Muscle Tissues
Tan, Y. H., Helms, H. R., & Nakayama, K. H. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.831300 · Cited by 47 · see citing works
Cell and organ bioengineering technology as applied to gastrointestinal diseases
Orlando, G., Bendala, J. D., Shupe, T., Bergman, C. R., Bitar, K., Booth, C., Carbone, M., Koch, K., Lerut, J., Neuberger, J., et al. (2012) · Gut · doi:10.1136/gutjnl-2011-301111 · Cited by 52 · see citing works
Liver-Regenerative Transplantation: Regrow and Reset
de l’Hortet, A. C., Takeishi, K., Guzman‐Lepe, J., Handa, K., Matsubara, K., Fukumitsu, K., Dorko, K., Presnell, S. C., Yagi, H., & Soto–Gutiérrez, A. (2015) · American Journal of Transplantation · doi:10.1111/ajt.13678 · Cited by 45 · see citing works
Self-citationTransforming healthcare through regenerative medicine
Jessop, Z. M., Al‐Sabah, A., Francis, W., & Whitaker, I. S. (2016) · BMC Medicine · doi:10.1186/s12916-016-0669-4 · Cited by 44 · see citing works
Cells and Materials for Liver Tissue Engineering
Li, Y.-S., Harn, H., Hsieh, D.-K., Wen, T.-C., Subeq, Y., Sun, L., Lin, S., & Chiou, T. (2013) · Cell Transplantation · doi:10.3727/096368912x655163 · Cited by 43 · see citing works
Enhanced reseeding of decellularized rodent lungs with mouse embryonic stem cells
Lecht, S., Stabler, C. T., Rylander, A. L., Chiaverelli, R. A., Schulman, E. S., Marcinkiewicz, C., & Lelkes, P. I. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.12.093 · Cited by 42 · see citing works
Caralt, M., Velasco, E., Lanas, Á., & Baptista, P. M. (2014) · Organogenesis · doi:10.4161/org.29892 · Cited by 42 · see citing works
- Authors
- Soto-Gutierrez, A., Zhang, L., Medberry, C., Fukumitsu, K., Faulk, D., Jiang, H., Reing, J., Gramignoli, R., Komori, J., Ross, M., Nagaya, M., Lagasse, E., Stolz, D., Strom, S. C., Fox, I. J., & Badylak, S. F.
- Affiliations
- Transplantation Section, Department of Surgery, Children's Hospital of Pittsburgh, Center for Innovative Regenerative Therapies, University of Pittsburgh, Pittsburgh, Pennsylvania.
- University of Pittsburgh (US)
- Corresponding author
- Badylak, Stephen F.
- ORCID
- Venue
- Tissue Engineering Part C: Methods
- Publisher
- SAGE Publications
- Published
- 2011-06
- Volume
- 17
- Issue
- 6
- Pages
- 677-686
- ISSN
- 1937-3384 (ISSN-L)
- 1937-3392
- PMC
- PMC3103054
- OpenAlex
- W2079165554
- Cited by
- 311
- References
- 32
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 10 · 2023: 12 · 2022: 12 · 2021: 18 · 2020: 14 · 2019: 21 · 2018: 24 · 2017: 33 · 2016: 32 · 2015: 32 · 2014: 35 · 2013: 24 · 2012: 25
- FWCI
- 29.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Tissue Engineering Part C Methods (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Liver Foundation
- National Institutes of Health (UL1TR000005)
- Japan Society for the Promotion of Science
- National Institute of Diabetes and Digestive and Kidney Diseases (K99DK083556, R00DK083556)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- liver tissue engineering, hepatocyte engraftment, extracellular matrix preservation, liver microvasculature, end-stage liver disease, albumin synthesis, urea metabolism, cytochrome P450 induction, cell therapy
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Male, Mice, Inbred C57BL, Organ Culture Techniques, Prosthesis Design, Rats, Sprague-Dawley, Liver, Artificial, Hepatocytes, Mice, Rats, Tissue Scaffolds
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