Organoids and regenerative hepatology.
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
01 01 2023
01 01 2023
Historique:
received:
15
02
2022
accepted:
14
05
2022
pubmed:
22
5
2022
medline:
13
1
2023
entrez:
21
5
2022
Statut:
ppublish
Résumé
The burden of liver diseases is increasing worldwide, with liver transplantation remaining the only treatment option for end-stage liver disease. Regenerative medicine holds great potential as a therapeutic alternative, aiming to repair or replace damaged liver tissue with healthy functional cells. The properties of the cells used are critical for the efficacy of this approach. The advent of liver organoids has not only offered new insights into human physiology and pathophysiology, but also provided an optimal source of cells for regenerative medicine and translational applications. Here, we discuss various historical aspects of 3D organoid culture, how it has been applied to the hepatobiliary system, and how organoid technology intersects with the emerging global field of liver regenerative medicine. We outline the hepatocyte, cholangiocyte, and nonparenchymal organoids systems available and discuss their advantages and limitations for regenerative medicine as well as future directions.
Identifiants
pubmed: 35596930
pii: 01515467-202301000-00028
doi: 10.1002/hep.32583
pmc: PMC9676408
mid: NIHMS1821807
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
305-322Subventions
Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : P30 DK084567
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117861
Pays : United States
Organisme : Medical Research Council
ID : MR/V023004/1
Pays : United Kingdom
Informations de copyright
Copyright © 2022 American Association for the Study of Liver Diseases.
Références
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: liver transplantation. J Hepatol. 2016;64:433–85.
Martin P, DiMartini A, Feng S, Brown R Jr, Fallon M. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014;59:1144–65.
Choi TY, Ninov N, Stainier DY, Shin D. Extensive conversion of hepatic biliary epithelial cells to hepatocytes after near total loss of hepatocytes in zebrafish. Gastroenterology. 2014;146:776–88.
He J, Lu H, Zou Q, Luo L. Regeneration of liver after extreme hepatocyte loss occurs mainly via biliary transdifferentiation in zebrafish. Gastroenterology. 2014;146:789–800.e8.
De Assuncao TM, Jalan‐Sakrikar N, Huebert RC. Regenerative medicine and the biliary tree. Semin Liver Dis. 2017;37:17–27.
Nelson TJ, Behfar A, Terzic A. Strategies for therapeutic repair: the “R(3)” regenerative medicine paradigm. Clin Transl Sci. 2008;1:168–71.
Atala A. Advances in tissue and organ replacement. Curr Stem Cell Res Ther. 2008;3:21–31.
Mavila N, Trecartin A, Spurrier R, Xiao Y, Hou X, James D, et al. Functional human and murine tissue‐engineered liver is generated from adult stem/progenitor cells. Stem Cells Transl Med. 2016;6:238–48.
Korbling M, Estrov Z. Adult stem cells for tissue repair—a new therapeutic concept? N Engl J Med. 2003;349:570–82.
Nicolas CT, Wang Y, Nyberg SL. Cell therapy in chronic liver disease. Curr Opin Gastroenterol. 2016;32:189–94.
Huebert RC, Rakela J. Cellular therapy for liver disease. Mayo Clin Proc. 2014;89:414–24.
Surani MA, McLaren A. Stem cells: a new route to rejuvenation. Nature. 2006;443:284–5.
Basu J, Ludlow JW. Exosomes for repair, regeneration and rejuvenation. Expert Opin Biol Ther. 2016;16:489–506.
Conboy IM, Conboy MJ, Rebo J. Systemic problems: a perspective on stem cell aging and rejuvenation. Aging. 2015;7:754–65.
Dhawan A, Mitry RR, Hughes RD, Lehec S, Terry C, Bansal S, et al. Hepatocyte transplantation for inherited factor VII deficiency. Transplantation. 2004;78:1812–4.
Dhawan A, Puppi J, Hughes RD, Mitry RR. Human hepatocyte transplantation: current experience and future challenges. Nat Rev Gastroenterol Hepatol. 2010;7:288–98.
El Agha E, Kramann R, Schneider RK, Li X, Seeger W, Humphreys BD, et al. Mesenchymal stem cells in fibrotic disease. Cell Stem Cell. 2017;21:166–77.
Houlihan DD, Newsome PN. Critical review of clinical trials of bone marrow stem cells in liver disease. Gastroenterology. 2008;135:438–50.
Nevens F, Gustot T, Laterre PF, Lasser LL, Haralampiev LE, Vargas V, et al. A phase II study of human allogeneic liver‐derived progenitor cell therapy for acute‐on‐chronic liver failure and acute decompensation. JHEP Rep. 2021;3:100291.
Dhawan A, Chaijitraruch N, Fitzpatrick E, Bansal S, Filippi C, Lehec SC, et al. Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children. J Hepatol. 2020;72:877–84.
Wang LJ, Chen YM, George D, Smets F, Sokal EM, Bremer EG, et al. Engraftment assessment in human and mouse liver tissue after sex‐mismatched liver cell transplantation by real‐time quantitative PCR for Y chromosome sequences. Liver Transpl. 2002;8:822–8.
Chiesa S, Morbelli S, Morando S, Massollo M, Marini C, Bertoni A, et al. Mesenchymal stem cells impair in vivo T‐cell priming by dendritic cells. Proc Natl Acad Sci U S A. 2011;108:17384–9.
Lo Sicco C, Reverberi D, Balbi C, Ulivi V, Principi E, Pascucci L, et al. Mesenchymal stem cell‐derived extracellular vesicles as mediators of anti‐inflammatory effects: endorsement of macrophage polarization. Stem Cells Transl Med. 2017;6:1018–28.
Christ B, Stock P. Mesenchymal stem cell‐derived hepatocytes for functional liver replacement. Front Immunol. 2012;3:168.
Gao J, Dennis JE, Muzic RF, Lundberg M, Caplan AI. The dynamic in vivo distribution of bone marrow‐derived mesenchymal stem cells after infusion. Cells Tissues Organs. 2001;169:12–20.
Berishvili E, Casiraghi F, Amarelli C, Scholz H, Piemonti L, Berney T, et al. Mini‐organs forum: how to advance organoid technology to organ transplant community. Transpl Int. 2021;34:1588–93.
Trowell OA. A modified technique for organ culture in vitro. Exp Cell Res. 1954;6:246–8.
Strangeways TS, Canti RG. Dark‐ground illumination of tissue cells cultivated “in vitro”. Br Med J. 1926;2:155–7.
Foty R. A simple hanging drop cell culture protocol for generation of 3D spheroids. J Vis Exp. 2011;(51):2720.
Ravi M, Paramesh V, Kaviya SR, Anuradha E, Solomon FD. 3D cell culture systems: advantages and applications. J Cell Physiol. 2015;230:16–26.
Li ML, Aggeler J, Farson DA, Hatier C, Hassell J, Bissell MJ. Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells. Proc Natl Acad Sci U S A. 1987;84:136–40.
Shannon JM, Mason RJ, Jennings SD. Functional differentiation of alveolar type II epithelial cells in vitro: effects of cell shape, cell‐matrix interactions and cell‐cell interactions. Biochim Biophys Acta. 1987;931:143–56.
Eiraku M, Watanabe K, Matsuo‐Takasaki M, Kawada M, Yonemura S, Matsumura M, et al. Self‐organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell. 2008;3:519–32.
Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, et al. Single Lgr5 stem cells build crypt‐villus structures in vitro without a mesenchymal niche. Nature. 2009;459:262–5.
Michalopoulos G, Pitot HC. Primary culture of parenchymal liver cells on collagen membranes. Morphological and biochemical observations. Exp Cell Res. 1975;94:70–8.
Landry J, Bernier D, Ouellet C, Goyette R, Marceau N. Spheroidal aggregate culture of rat liver cells: histotypic reorganization, biomatrix deposition, and maintenance of functional activities. J Cell Biol. 1985;101:914–23.
Takezawa T, Yamazaki M, Mori Y, Yonaha T, Yoshizato K. Morphological and immuno‐cytochemical characterization of a hetero‐spheroid composed of fibroblasts and hepatocytes. J Cell Sci. 1992;101(Pt 3):495–501.
Saito S, Sakagami K, Matsuno T, Tanakaya K, Takaishi Y, Orita K. Long‐term survival and proliferation of spheroidal aggregate cultured hepatocytes transplanted into the rat spleen. Transplant Proc. 1992;24:1520–1.
Nyberg SL, Peshwa MV, Payne WD, Hu WS, Cerra FB. Evolution of the bioartificial liver: the need for randomized clinical trials. Am J Surg. 1993;166:512–21.
Banales JM, Masyuk TV, Bogert PS, Huang BQ, Gradilone SA, Lee SO, et al. Hepatic cystogenesis is associated with abnormal expression and location of ion transporters and water channels in an animal model of autosomal recessive polycystic kidney disease. Am J Pathol. 2008;173:1637–46.
Muff MA, Masyuk TV, Stroope AJ, Huang BQ, Splinter PL, Lee SO, et al. Development and characterization of a cholangiocyte cell line from the PCK rat, an animal model of autosomal recessive polycystic kidney disease. Lab Invest. 2006;86:940–50.
Clevers H. Modeling development and disease with organoids. Cell. 2016;165:1586–97.
Marsee A, Roos FJM, Verstegen MMA, Consortium HPBO, Gehart H, de Koning E, et al. Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids. Cell Stem Cell. 2021;28:816–32.
Ober EA, Lemaigre FP. Development of the liver: insights into organ and tissue morphogenesis. J Hepatol. 2018;68:1049–62.
Lemaigre FP. Development of the intrahepatic and extrahepatic biliary tract: a framework for understanding congenital diseases. Annu Rev Pathol. 2020;15:1–22.
Michalopoulos GK, Bowen WC, Mule K, Stolz DB. Histological organization in hepatocyte organoid cultures. Am J Pathol. 2001;159:1877–87.
Huch M, Dorrell C, Boj SF, van Es JH, Li VS, van de Wetering M, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt‐driven regeneration. Nature. 2013;494:247–50.
Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen MM, et al. Long‐term culture of genome‐stable bipotent stem cells from adult human liver. Cell. 2015;160:299–312.
Peng WC, Logan CY, Fish M, Anbarchian T, Aguisanda F, Alvarez‐Varela A, et al. Inflammatory cytokine TNFalpha promotes the long‐term expansion of primary hepatocytes in 3D culture. Cell. 2018;175:1607–19.e15.
Hu H, Gehart H, Artegiani B, Lopez‐Iglesias C, Dekkers F, Basak O, et al. Long‐term expansion of functional mouse and human hepatocytes as 3D organoids. Cell. 2018;175:1591–606.e19.
Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, et al. Vascularized and functional human liver from an iPSC‐derived organ bud transplant. Nature. 2013;499:481–4.
Takebe T, Sekine K, Kimura M, Yoshizawa E, Ayano S, Koido M, et al. Massive and reproducible production of liver buds entirely from human pluripotent stem cells. Cell Rep. 2017;21:2661–70.
Kruitwagen HS, Oosterhoff LA, Vernooij I, Schrall IM, van Wolferen ME, Bannink F, et al. Long‐term adult feline liver organoid cultures for disease modeling of hepatic steatosis. Stem Cell Reports. 2017;8:822–30.
Kuijk EW, Rasmussen S, Blokzijl F, Huch M, Gehart H, Toonen P, et al. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure. Sci Rep. 2016;6:22154.
Nantasanti S, Spee B, Kruitwagen HS, Chen C, Geijsen N, Oosterhoff LA, et al. Disease modeling and gene therapy of copper storage disease in canine hepatic organoids. Stem Cell Reports. 2015;5:895–907.
Sampaziotis F, de Brito MC, Madrigal P, Bertero A, Saeb‐Parsy K, Soares FAC, et al. Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nat Biotechnol. 2015;33:845–52.
Broutier L, Mastrogiovanni G, Verstegen MM, Francies HE, Gavarro LM, Bradshaw CR, et al. Human primary liver cancer‐derived organoid cultures for disease modeling and drug screening. Nat Med. 2017;23:1424–35.
Guan Y, Xu D, Garfin PM, Ehmer U, Hurwitz M, Enns G, et al. Human hepatic organoids for the analysis of human genetic diseases. JCI Insight. 2017;2:e94954.
Wu F, Wu D, Ren Y, Huang Y, Feng B, Zhao N, et al. Generation of hepatobiliary organoids from human induced pluripotent stem cells. J Hepatol. 2019;70:1145–58.
Akbari S, Sevinc GG, Ersoy N, Basak O, Kaplan K, Sevinc K, et al. Robust, long‐term culture of endoderm‐derived hepatic organoids for disease modeling. Stem Cell Reports. 2019;13:627–41.
Tanimizu N, Ichinohe N, Sasaki Y, Itoh T, Sudo R, Yamaguchi T, et al. Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo. Nat Commun. 2021;12:3390.
Koike H, Iwasawa K, Ouchi R, Maezawa M, Giesbrecht K, Saiki N, et al. Modelling human hepato‐biliary‐pancreatic organogenesis from the foregut‐midgut boundary. Nature. 2019;574:112–6.
Brevini T, Tysoe OC, Sampaziotis F. Tissue engineering of the biliary tract and modelling of cholestatic disorders. J Hepatol. 2020;73:918–32.
Banales JM, Huebert RC, Karlsen T, Strazzabosco M, LaRusso NF, Gores GJ. Cholangiocyte pathobiology. Nat Rev Gastroenterol Hepatol. 2019;16:269–81.
Boyer JL. Bile formation and secretion. Compr Physiol. 2013;3:1035–78.
Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis—a comprehensive review. J Hepatol. 2017;67:1298–323.
De Assuncao TM, Sun Y, Jalan‐Sakrikar N, Drinane MC, Huang BQ, Li Y, et al. Development and characterization of human‐induced pluripotent stem cell‐derived cholangiocytes. Lab Invest. 2015;95:684–96.
Dianat N, Dubois‐Pot‐Schneider H, Steichen C, Desterke C, Leclerc P, Raveux A, et al. Generation of functional cholangiocyte‐like cells from human pluripotent stem cells and HepaRG cells. Hepatology. 2014;60:700–14.
Jalan‐Sakrikar N, De Assuncao TM, Navarro‐Corcuera A, Hamdan FH, Loarca L, Kirkeby LA, et al. Induced pluripotent stem cells from subjects with primary sclerosing cholangitis develop a senescence phenotype following biliary differentiation. Hepatol Commun. 2022;6:345–60.
Ogawa M, Jiang JX, Xia S, Yang D, Ding A, Laselva O, et al. Generation of functional ciliated cholangiocytes from human pluripotent stem cells. Nat Commun. 2021;12:6504.
Ogawa M, Ogawa S, Bear CE, Ahmadi S, Chin S, Li B, et al. Directed differentiation of cholangiocytes from human pluripotent stem cells. Nat Biotechnol. 2015;33:853–61.
Si‐Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and development of the liver. Dev Cell. 2010;18:175–89.
Takayama K, Mitani S, Nagamoto Y, Sakurai F, Tachibana M, Taniguchi Y, et al. Laminin 411 and 511 promote the cholangiocyte differentiation of human induced pluripotent stem cells. Biochem Biophys Res Commun. 2016;474:91–6.
Hartman BH, Reh TA, Bermingham‐McDonogh O. Notch signaling specifies prosensory domains via lateral induction in the developing mammalian inner ear. Proc Natl Acad Sci U S A. 2010;107:15792–7.
Okabe H, Yang J, Sylakowski K, Yovchev M, Miyagawa Y, Nagarajan S, et al. Wnt signaling regulates hepatobiliary repair following cholestatic liver injury in mice. Hepatology. 2016;64:1652–66.
Aloia L, McKie MA, Vernaz G, Cordero‐Espinoza L, Aleksieva N, van den Ameele J, et al. Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration. Nat Cell Biol. 2019;21:1321–33.
Sampaziotis F, Justin AW, Tysoe OC, Sawiak S, Godfrey EM, Upponi SS, et al. Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nat Med. 2017;23:954–63.
Tysoe OC, Justin AW, Brevini T, Chen SE, Mahbubani KT, Frank AK, et al. Isolation and propagation of primary human cholangiocyte organoids for the generation of bioengineered biliary tissue. Nat Protoc. 2019;14:1884–925.
Sampaziotis F, Muraro D, Tysoe OC, Sawiak S, Beach TE, Godfrey EM, et al. Cholangiocyte organoids can repair bile ducts after transplantation in the human liver. Science. 2021;371:839–46.
Gunther C, Brevini T, Sampaziotis F, Neurath MF. What gastroenterologists and hepatologists should know about organoids in 2019. Dig Liver Dis. 2019;51:753–60.
Soroka CJ, Assis DN, Alrabadi LS, Roberts S, Cusack L, Jaffe AB, et al. Bile‐derived organoids from patients with primary sclerosing cholangitis recapitulate their inflammatory immune profile. Hepatology. 2019;70:871–82.
Amarachintha SP, Mourya R, Ayabe H, Yang L, Luo Z, Li X, et al. Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia. Hepatology. 2022;75:89–103.
Koui Y, Kido T, Ito T, Oyama H, Chen SW, Katou Y, et al. An in vitro human liver model by iPSC‐derived parenchymal and non‐parenchymal cells. Stem Cell Reports. 2017;9:490–8.
Coll M, Perea L, Boon R, Leite SB, Vallverdú J, Mannaerts I, et al. Generation of hepatic stellate cells from human pluripotent stem cells enables in vitro modeling of liver fibrosis. Cell Stem Cell. 2018;23:101–13.e7.
Ouchi R, Togo S, Kimura M, Shinozawa T, Koido M, Koike H, et al. Modeling steatohepatitis in humans with pluripotent stem cell‐derived organoids. Cell Metab. 2019;30:374–84.e6.
Meran L, Massie I, Campinoti S, Weston AE, Gaifulina R, Tullie L, et al. Engineering transplantable jejunal mucosal grafts using patient‐derived organoids from children with intestinal failure. Nat Med. 2020;26:1593–601.
Sampaziotis F, Segeritz CP, Vallier L. Potential of human induced pluripotent stem cells in studies of liver disease. Hepatology. 2015;62:303–11.
Lendahl U, Lui VCH, Chung PHY, Tam PKH. Biliary atresia—emerging diagnostic and therapy opportunities. EBioMedicine. 2021;74:103689.
Spada M, Riva S, Maggiore G, Cintorino D, Gridelli B. Pediatric liver transplantation. World J Gastroenterol. 2009;15:648–74.
Gieseck RL 3rd, Hannan NR, Bort R, Hanley NA, Drake RA, Cameron GW, et al. Maturation of induced pluripotent stem cell derived hepatocytes by 3D‐culture. PLoS One. 2014;9:e86372.
Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, et al. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. Nat Med. 2012;18:618–23.
Hofer M, Lutolf MP. Engineering organoids. Nat Rev Mater. 2021;6:402–20.
Przepiorski A, Sander V, Tran T, Hollywood JA, Sorrenson B, Shih JH, et al. A simple bioreactor‐based method to generate kidney organoids from pluripotent stem cells. Stem Cell Reports. 2018;11:470–84.
Kozlowski MT, Crook CJ, Ku HT. Towards organoid culture without Matrigel. Commun Biol. 2021;4:1387.
Gjorevski N, Sachs N, Manfrin A, Giger S, Bragina ME, Ordonez‐Moran P, et al. Designer matrices for intestinal stem cell and organoid culture. Nature. 2016;539:560–4.
Sorrentino G, Rezakhani S, Yildiz E, Nuciforo S, Heim MH, Lutolf MP, et al. Mechano‐modulatory synthetic niches for liver organoid derivation. Nat Commun. 2020;11:3416.
Wang Y, Lee JH, Shirahama H, Seo J, Glenn JS, Cho NJ. Extracellular matrix functionalization and Huh‐7.5 cell coculture promote the hepatic differentiation of human adipose‐derived mesenchymal stem cells in a 3D ICC hydrogel scaffold. ACS Biomater Sci Eng. 2016;2:2255–65.
Giobbe GG, Crowley C, Luni C, Campinoti S, Khedr M, Kretzschmar K, et al. Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture. Nat Commun. 2019;10:5658.
Lewis PL, Su J, Yan M, Meng F, Glaser SS, Alpini GD, et al. Complex bile duct network formation within liver decellularized extracellular matrix hydrogels. Sci Rep. 2018;8:12220.
Ng SS, Saeb‐Parsy K, Blackford SJI, Segal JM, Serra MP, Horcas‐Lopez M, et al. Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold. Biomaterials. 2018;182:299–311.
Aisenbrey EA, Murphy WL. Synthetic alternatives to Matrigel. Nat Rev Mater. 2020;5:539–51.
Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta‐analysis of clinical trials. PLoS One. 2012;7:e47559.
Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, et al. Mesenchymal stem cells for treatment of steroid‐resistant, severe, acute graft‐versus‐host disease: a phase II study. Lancet. 2008;371:1579–86.
Manji RA, Lee W, Cooper DKC. Xenograft bioprosthetic heart valves: past, present and future. Int J Surg. 2015;23:280–4.
Mazza G, Al‐Akkad W, Telese A, Longato L, Urbani L, Robinson B, et al. Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation‐decellularization. Sci Rep. 2017;7:5534.
Mazza G, Rombouts K, Rennie Hall A, Urbani L, Vinh Luong T, Al‐Akkad W, et al. Decellularized human liver as a natural 3D‐scaffold for liver bioengineering and transplantation. Sci Rep. 2015;5:13079.
Roos FJM, Wu H, Willemse J, Lieshout R, Albarinos LAM, Kan YY, et al. Cholangiocyte organoids from human bile retain a local phenotype and can repopulate bile ducts in vitro. Clin Transl Med. 2021;11:e566.
Willemse J, Roos FJM, Voogt IJ, Schurink IJ, Bijvelds M, de Jonge HR, et al. Scaffolds obtained from decellularized human extrahepatic bile ducts support organoids to establish functional biliary tissue in a dish. Biotechnol Bioeng. 2021;118:836–51.
Shaheen MF, Joo DJ, Ross JJ, Anderson BD, Chen HS, Huebert RC, et al. Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs. Nat Biomed Eng. 2020;4:437–45.
Brassard JA, Nikolaev M, Hubscher T, Hofer M, Lutolf MP. Recapitulating macro‐scale tissue self‐organization through organoid bioprinting. Nat Mater. 2021;20:22–9.
Xu H, Wang B, Ono M, Kagita A, Fujii K, Sasakawa N, et al. Targeted disruption of HLA genes via CRISPR‐Cas9 generates iPSCs with enhanced immune compatibility. Cell Stem Cell. 2019;24:566–78.e7.
Yoshihara E, O'Connor C, Gasser E, Wei Z, Oh TG, Tseng TW, et al. Immune‐evasive human islet‐like organoids ameliorate diabetes. Nature. 2020;586:606–11.
Saito R, Ishii Y, Ito R, Nagatsuma K, Tanaka K, Saito M, et al. Transplantation of liver organoids in the omentum and kidney. Artif Organs. 2011;35:80–3.
Nie YZ, Zheng YW, Ogawa M, Miyagi E, Taniguchi H. Human liver organoids generated with single donor‐derived multiple cells rescue mice from acute liver failure. Stem Cell Res Ther. 2018;9:5.
Stevens KR, Scull MA, Ramanan V, Fortin CL, Chaturvedi RR, Knouse KA, et al. In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease. Sci Transl Med. 2017;9:eaah5505.
Pettinato G, Lehoux S, Ramanathan R, Salem MM, He LX, Muse O, et al. Generation of fully functional hepatocyte‐like organoids from human induced pluripotent stem cells mixed with endothelial cells. Sci Rep. 2019;9:8920.
Yap KK, Gerrand YW, Dingle AM, Yeoh GC, Morrison WA, Mitchell GM. Liver sinusoidal endothelial cells promote the differentiation and survival of mouse vascularised hepatobiliary organoids. Biomaterials. 2020;251:120091.
Tsuchida T, Murata S, Matsuki K, Mori A, Matsuo M, Mikami S, et al. The regenerative effect of portal vein injection of liver organoids by retrorsine/partial hepatectomy in rats. Int J Mol Sci. 2019;21:178.
Tsuchida T, Murata S, Hasegawa S, Mikami S, Enosawa S, Hsu HC, et al. Investigation of clinical safety of human iPS cell‐derived liver organoid transplantation to infantile patients in porcine model. Cell Transplant. 2020;29:963689720964384.
Zhang RR, Koido M, Tadokoro T, Ouchi R, Matsuno T, Ueno Y, et al. Human iPSC‐derived posterior gut progenitors are expandable and capable of forming gut and liver organoids. Stem Cell Reports. 2018;10:780–93.