Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-30T07:44:15.511Z Has data issue: false hasContentIssue false

Take a deep breath and digest the material: organoids and biomaterials of the respiratory and digestive systems

Published online by Cambridge University Press:  14 August 2017

Briana R. Dye
Affiliation:
Biomedical Engineering, University of Michigan Biomedical Engineering, Ann Arbor, Michigan 48109, USA
Tadas Kasputis
Affiliation:
Biomedical Engineering, University of Michigan Biomedical Engineering, Ann Arbor, Michigan 48109, USA
Jason R. Spence
Affiliation:
Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA Department of Cell and Developmental Biology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA Center of Organogenesis, Michigan Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
Lonnie D. Shea*
Affiliation:
Biomedical Engineering, University of Michigan Biomedical Engineering, Ann Arbor, Michigan 48109, USA
*
Address all correspondence to Lonnie D. Shea at [email protected]
Get access

Abstract

Human organoid models recapitulate many aspects of the complex composition and function of native organs. One of the main challenges in developing these models is the growth and maintenance of three-dimensional tissue structures and proper cellular organization that enable function. Biomaterials play an important role by providing a defined and tunable three-dimensional environment that is required for complex cellular organization and organoid growth in vitro or in vivo. This review summarizes organoids of the respiratory and digestive system, and the use of biomaterials to improve upon these model systems.

Type
Biomaterials for 3D Cell Biology Prospective Article
Copyright
Copyright © Materials Research Society 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Miller, A.J. and Spence, J.R.: In vitro models to study human lung development, disease and homeostasis. Physiology (Bethesda) 32, 246260 (2017).Google Scholar
2.Aurora, M. and Spence, J.R.: hPSC-derived lung and intestinal organoids as models of human fetal tissue. Dev. Biol. 420, 230238 (2016).Google Scholar
3.Kim, G.-A., Spence, J.R., and Takayama, S.: Bioengineering for intestinal organoid cultures. Curr. Opin. Biotechnol. 47, 5158 (2017).Google Scholar
4.Dye, B.R., Miller, A.J., and Spence, J.R.: How to grow a lung: applying principles of developmental biology to generate lung lineages from human pluripotent stem cells. Curr. Pathobiol. Rep. 4, 4757 (2016).Google Scholar
5.Clevers, H.: Modeling development and disease with organoids. Cell 165, 15861597 (2016).Google Scholar
6.Bartfeld, S. and Clevers, H.: Stem cell-derived organoids and their application for medical research and patient treatment. J. Mol. Med. 95, 729738 (2017).Google Scholar
7.Drost, J. and Clevers, H.: Translational applications of adult stem cell-derived organoids. Development 144, 968975 (2017).Google Scholar
8.Dedhia, P.H., Bertaux-Skeirik, N., Zavros, Y., and Spence, J.R.: Organoid models of human gastrointestinal development and disease. Gastroenterology 150, 10981112 (2016).Google Scholar
9.Fatehullah, A., Tan, S.H., and Barker, N.: Organoids as an in vitro model of human development and disease. Nat. Cell Biol. 18, 246254 (2016).Google Scholar
10.Johnson, J.Z. and Hockemeyer, D.: Human stem cell-based disease modeling: prospects and challenges. Curr. Opin. Cell Biol. 37, 8490 (2015).Google Scholar
11.Huch, M. and Koo, B.-K.: Modeling mouse and human development using organoid cultures. Development 142, 31133125 (2015).Google Scholar
12.Rookmaaker, M.B., Schutgens, F., Verhaar, M.C., and Clevers, H.: Development and application of human adult stem or progenitor cell organoids. Nat. Rev. Nephrol. 11, 546554 (2015).Google Scholar
13.Shamir, E.R. and Ewald, A.J.: Three-dimensional organotypic culture: experimental models of mammalian biology and disease. Nat. Rev. Mol. Cell Biol. 15, 647664 (2014).Google Scholar
14.Sato, T., Stange, D.E., Ferrante, M., Vries, R.G.J., van Es, J.H., Van den Brink, S., Van Houdt, W.J., Pronk, A., Van Gorp, J., Siersema, P.D., and Clevers, H.: Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 141, 17621772 (2011).Google Scholar
15.Sato, T. and Clevers, H.: Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340, 11901194 (2013).Google Scholar
16.Mahe, M.M., Sundaram, N., Watson, C.L., Shroyer, N.F., and Helmrath, M.A.: Establishment of human epithelial enteroids and colonoids from whole tissue and biopsy. J. Vis. Exp. (97) (2015).Google Scholar
17.Jabaji, Z., Brinkley, G.J., Khalil, H.A., Sears, C.M., Lei, N.Y., Lewis, M., Stelzner, M., Martin, M.G., and Dunn, J.C.Y.: Type I collagen as an extracellular matrix for the in vitro growth of human small intestinal epithelium. PLoS ONE 9, e107814 (2014).Google Scholar
18.Gjorevski, N., Sachs, N., Manfrin, A., Giger, S., Bragina, M.E., Ordóñez-Morán, P., Clevers, H., and Lutolf, M.P.: Designer matrices for intestinal stem cell and organoid culture. Nature 539, 560564 (2016).Google Scholar
19.Spence, J.R., Mayhew, C.N., Rankin, S.A., Kuhar, M.F., Vallance, J.E., Tolle, K., Hoskins, E.E., Kalinichenko, V.V., Wells, S.I., Zorn, A.M., Shroyer, N.F., and Wells, J.M.: Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470, 105109 (2011).Google Scholar
20.Wells, J.M. and Spence, J.R.: How to make an intestine. Development 141, 752760 (2014).Google Scholar
21.Finkbeiner, S.R., Freeman, J.J., Wieck, M.M., El-Nachef, W., Altheim, C.H., Tsai, Y.-H., Huang, S., Dyal, R., White, E.S., Grikscheit, T.C., Teitelbaum, D.H., and Spence, J.R.: Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoids. Biol. Open 4, 14621472 (2015).Google Scholar
22.Watson, C.L., Mahe, M.M., Múnera, J., Howell, J.C., Sundaram, N., Poling, H.M., Schweitzer, J.I., Vallance, J.E., Mayhew, C.N., Sun, Y., Grabowski, G., Finkbeiner, S.R., Spence, J.R., Shroyer, N.F., Wells, J.M., and Helmrath, M.A.: An in vivo model of human small intestine using pluripotent stem cells. Nat. Med. 20, 13101314 (2014).Google Scholar
23.Finkbeiner, S.R., Zeng, X.-L., Utama, B., Atmar, R.L., Shroyer, N.F., and Estes, M.K.: Stem cell-derived human intestinal organoids as an infection model for rotaviruses. mBio 3, e0015912 (2012).Google Scholar
24.Leslie, J.L., Huang, S., Opp, J.S., Nagy, M.S., Kobayashi, M., Young, V.B., and Spence, J.R.: Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function. Infect. Immun. 83, 138145 (2015).Google Scholar
25.Kovbasnjuk, O., Zachos, N.C., In, J., Foulke-Abel, J., Ettayebi, K., Hyser, J.M., Broughman, J.R., Zeng, X.-L., Middendorp, S., de Jonge, H.R., Estes, M.K., and Donowitz, M.: Human enteroids: preclinical models of non-inflammatory diarrhea. Stem Cell Res. Ther. 4(Suppl. 1), S3 (2013).Google Scholar
26.Fujii, M., Shimokawa, M., Date, S., Takano, A., Matano, M., Nanki, K., Ohta, Y., Toshimitsu, K., Nakazato, Y., Kawasaki, K., Uraoka, T., Watanabe, T., Kanai, T., and Sato, T.: A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 18, 827838 (2016).Google Scholar
27.Cristobal, A., van den Toorn, H.W.P., van de Wetering, M., Clevers, H., Heck, A.J.R., and Mohammed, S.: Personalized proteome profiles of healthy and tumor human colon organoids reveal both individual diversity and basic features of colorectal cancer. Cell Rep. 18, 263274 (2017).Google Scholar
28.Matano, M., Date, S., Shimokawa, M., Takano, A., Fujii, M., Ohta, Y., Watanabe, T., Kanai, T., and Sato, T.: Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat. Med. 21, 256262 (2015).Google Scholar
29.Drost, J., van Jaarsveld, R.H., Ponsioen, B., Zimberlin, C., van Boxtel, R., Buijs, A., Sachs, N., Overmeer, R.M., Offerhaus, G.J., Begthel, H., Korving, J., van de Wetering, M., Schwank, G., Logtenberg, M., Cuppen, E., Snippert, H.J., Medema, J.P., Kops, G.J.P.L., and Clevers, H.: Sequential cancer mutations in cultured human intestinal stem cells. Nature 521, 4347 (2015).Google Scholar
30.Fumagalli, A., Drost, J., Suijkerbuijk, S.J.E., van Boxtel, R., de Ligt, J., Offerhaus, G.J., Begthel, H., Beerling, E., Tan, E.H., Sansom, O.J., Cuppen, E., Clevers, H., and van Rheenen, J.: Genetic dissection of colorectal cancer progression by orthotopic transplantation of engineered cancer organoids. Proc. Natl. Acad. Sci. USA 114, E2357E2364 (2017).Google Scholar
31.Shimokawa, M., Ohta, Y., Nishikori, S., Matano, M., Takano, A., Fujii, M., Date, S., Sugimoto, S., Kanai, T., and Sato, T.: Visualization and targeting of LGR5(+) human colon cancer stem cells. Nature 545, 187192 (2017).Google Scholar
32.Mizutani, T., Tsukamoto, Y., and Clevers, H.: Oncogene-inducible organoids as a miniature platform to assess cancer characteristics. J. Cell Biol. 216, 15051507 (2017).Google Scholar
33.Jung, P., Sato, T., Merlos-Suárez, A., Barriga, F.M., Iglesias, M., Rossell, D., Auer, H., Gallardo, M., Blasco, M.A., Sancho, E., Clevers, H., and Batlle, E.: Isolation and in vitro expansion of human colonic stem cells. Nat. Med. 17, 12251227 (2011).Google Scholar
34.Dekkers, J.F., Berkers, G., Kruisselbrink, E., Vonk, A., de Jonge, H.R., Janssens, H.M., Bronsveld, I., van de Graaf, E.A., Nieuwenhuis, E.E.S., Houwen, R.H.J., Vleggaar, F.P., Escher, J.C., de Rijke, Y.B., Majoor, C.J., Heijerman, H.G.M., de Winter-de Groot, K.M., Clevers, H., van der Ent, C.K., and Beekman, J.M.: Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis. Sci. Transl. Med. 8, 344ra84344ra84 (2016).Google Scholar
35.Vijftigschild, L.A.W., Berkers, G., Dekkers, J.F., Zomer-van Ommen, D.D., Matthes, E., Kruisselbrink, E., Vonk, A., Hensen, C.E., Heida-Michel, S., Geerdink, M., Janssens, H.M., van de Graaf, E.A., Bronsveld, I., de Winter-de Groot, K.M., Majoor, C.J., Heijerman, H.G.M., de Jonge, H.R., Hanrahan, J.W., van der Ent, C.K., and Beekman, J.M.: β2-Adrenergic receptor agonists activate CFTR in intestinal organoids and subjects with cystic fibrosis. Eur. Respir. J. 48, 768779 (2016).Google Scholar
36.van de Wetering, M., Francies, H.E., Francis, J.M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., Van Gorp, J., Taylor-Weiner, A., Kester, L., McLaren-Douglas, A., Blokker, J., Jaksani, S., Bartfeld, S., Volckman, R., van Sluis, P., Li, V.S.W., Seepo, S., Sekhar Pedamallu, C., Cibulskis, K., Carter, S.L., McKenna, A., Lawrence, M.S., Lichtenstein, L., Stewart, C., Koster, J., Versteeg, R., van Oudenaarden, A., Saez-Rodriguez, J., Vries, R.G.J., Getz, G., Wessels, L., Stratton, M.R., McDermott, U., Meyerson, M., Garnett, M.J., and Clevers, H.: Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161, 933945 (2015).Google Scholar
37.Czerwinski, M. and Spence, J.R.: Hacking the matrix. Cell Stem Cell 20, 910 (2017).Google Scholar
38.Hughes, C.S., Postovit, L.M., and Lajoie, G.A.: Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10, 18861890 (2010).Google Scholar
39.Finkbeiner, S.R. and Spence, J.R.: A gutsy task: generating intestinal tissue from human pluripotent stem cells. Dig. Dis. Sci. 58, 11761184 (2013).Google Scholar
40.Finkbeiner, S.R., Hill, D.R., Altheim, C.H., Dedhia, P.H., Taylor, M.J., Tsai, Y.-H., Chin, A.M., Mahe, M.M., Watson, C.L., Freeman, J.J., Nattiv, R., Thomson, M., Klein, O.D., Shroyer, N.F., Helmrath, M.A., Teitelbaum, D.H., Dempsey, P.J., and Spence, J.R.: Transcriptome-wide analysis reveals hallmarks of human intestine development and maturation in vitro and in vivo. Stem Cell Rep. 4, 11401155 (2015).Google Scholar
41.Tsai, Y.-H., Nattiv, R., Dedhia, P.H., Nagy, M.S., Chin, A.M., Thomson, M., Klein, O.D., and Spence, J.R.: In vitro patterning of pluripotent stem cell-derived intestine recapitulates in vivo human development. Development 144, 10451055 (2017).Google Scholar
42.Mojibian, M., Glavas, M.M., and Kieffer, T.J.: Engineering the gut for insulin replacement to treat diabetes. J. Diab. Investig. 7(Suppl. 1), 8793 (2016).Google Scholar
43.Melton, D.A.: Applied developmental biology: making human pancreatic beta cells for diabetics. Curr. Top. Dev. Biol. 117, 6573 (2016).Google Scholar
44.Quiskamp, N., Bruin, J.E., and Kieffer, T.J.: Differentiation of human pluripotent stem cells into β-cells: potential and challenges. Best Pract. Res. Clin. Endocrinol. Metab. 29, 833847 (2015).Google Scholar
45.Loo, L.S.W., Lau, H.H., Jasmen, J.B., Lim, C.S., and Teo, A.K.K.: An arduous journey from human pluripotent stem cells to functional pancreatic β cells. Diab. Obes. Metab. 355, 1318 (2017).Google Scholar
46.Cryer, P.E.: The barrier of hypoglycemia in diabetes. Diabetes 57, 31693176 (2008).Google Scholar
47.Pambianco, G., Costacou, T., Ellis, D., Becker, D.J., Klein, R., and Orchard, T.J.: The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience. Diabetes 55, 14631469 (2006).Google Scholar
48.Barton, F.B., Rickels, M.R., Alejandro, R., Hering, B.J., Wease, S., Naziruddin, B., Oberholzer, J., Odorico, J.S., Garfinkel, M.R., Levy, M., Pattou, F., Berney, T., Secchi, A., Messinger, S., Senior, P.A., Maffi, P., Posselt, A., Stock, P.G., Kaufman, D.B., Luo, X., Kandeel, F., Cagliero, E., Turgeon, N.A., Witkowski, P., Naji, A., O'Connell, P.J., Greenbaum, C., Kudva, Y.C., Brayman, K.L., Aull, M.J., Larsen, C., Kay, T.W.H., Fernandez, L.A., Vantyghem, M.-C., Bellin, M., and Shapiro, A.M.J.: Improvement in outcomes of clinical islet transplantation: 1999–2010. Diab. Care 35, 14361445 (2012).Google Scholar
49.Desai, T. and Shea, L.D.: Advances in islet encapsulation technologies. Nat. Rev. Drug Discov. 54, 2060 (2016).Google Scholar
50.Robertson, R.P.: Islet transplantation a decade later and strategies for filling a half-full glass. Diabetes 59, 12851291 (2010).Google Scholar
51.Kenyon, N.S., Chatzipetrou, M., Masetti, M., Ranuncoli, A., Oliveira, M., Wagner, J.L., Kirk, A.D., Harlan, D.M., Burkly, L.C., and Ricordi, C.: Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proc. Natl. Acad. Sci. USA 96, 81328137 (1999).Google Scholar
52.Srinivasan, P., Huang, G.C., Amiel, S.A., and Heaton, N.D.: Islet cell transplantation. Postgrad. Med. J. 83, 224229 (2007).Google Scholar
53.Pagliuca, F.W., Millman, J.R., Gürtler, M., Segel, M., Van Dervort, A., Ryu, J.H., Peterson, Q.P., Greiner, D., and Melton, D.A.: Generation of functional human pancreatic β cells in vitro. Cell 159, 428439 (2014).Google Scholar
54.Pagliuca, F.W., Melton, D.A.: How to make a functional β-cell. Development 140, 24722483 (2013).Google Scholar
55.Rezania, A., Bruin, J.E., Arora, P., Rubin, A., Batushansky, I., Asadi, A., O'Dwyer, S., Quiskamp, N., Mojibian, M., Albrecht, T., Yang, Y.H.C., Johnson, J.D., and Kieffer, T.J.: Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat. Biotechnol. 32, 11211133 (2014).Google Scholar
56.Rezania, A., Bruin, J.E., Riedel, M.J., Mojibian, M., Asadi, A., Xu, J., Gauvin, R., Narayan, K., Karanu, F., O'Neil, J.J., Ao, Z., Warnock, G.L., and Kieffer, T.J.: Maturation of human embryonic stem cell-derived pancreatic progenitors into functional islets capable of treating pre-existing diabetes in mice. Diabetes 61, 20162029 (2012).Google Scholar
57.Vegas, A.J., Veiseh, O., Gürtler, M., Millman, J.R., Pagliuca, F.W., Bader, A.R., Doloff, J.C., Li, J., Chen, M., Olejnik, K., Tam, H.H., Jhunjhunwala, S., Langan, E., Aresta-Dasilva, S., Gandham, S., McGarrigle, J.J., Bochenek, M.A., Hollister-Lock, J., Oberholzer, J., Greiner, D.L., Weir, G.C., Melton, D.A., Langer, R., and Anderson, D.G.: Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat. Med. 22, 306311 (2016).Google Scholar
58.Millman, J.R., Xie, C., Van Dervort, A., Gürtler, M., Pagliuca, F.W., and Melton, D.A.: Corrigendum: generation of stem cell-derived β-cells from patients with type 1 diabetes. Nat. Commun. 7, 12379 (2016).Google Scholar
59.Schulz, T.C., Young, H.Y., Agulnick, A.D., Babin, M.J., Baetge, E.E., Bang, A.G., Bhoumik, A., Cepa, I., Cesario, R.M., Haakmeester, C., Kadoya, K., Kelly, J.R., Kerr, J., Martinson, L.A., McLean, A.B., Moorman, M.A., Payne, J.K., Richardson, M., Ross, K.G., Sherrer, E.S., Song, X., Wilson, A.Z., Brandon, E.P., Green, C.E., Kroon, E.J., Kelly, O.G., D'Amour, K.A., and Robins, A.J.: A scalable system for production of functional pancreatic progenitors from human embryonic stem cells. PLoS ONE 7, e37004 (2012).Google Scholar
60.Kim, Y., Kim, H., Ko, U.H., Oh, Y., Lim, A., Sohn, J.-W., Shin, J.H., Kim, H., and Han, Y.-M.: Islet-like organoids derived from human pluripotent stem cells efficiently function in the glucose responsiveness in vitro and in vivo. Sci. Rep. 6, 35145 (2016).Google Scholar
61.Bosco, D., Armanet, M., Morel, P., Niclauss, N., Sgroi, A., Muller, Y.D., Giovannoni, L., Parnaud, G., and Berney, T.: Unique arrangement of alpha- and beta-cells in human islets of Langerhans. Diabetes 59, 12021210 (2010).Google Scholar
62.Gibly, R.F., Zhang, X., Graham, M.L., Hering, B.J., Kaufman, D.B., Lowe, W.L., and Shea, L.D.: Extrahepatic islet transplantation with microporous polymer scaffolds in syngeneic mouse and allogeneic porcine models. Biomaterials 32, 96779684 (2011).Google Scholar
63.Blomeier, H., Zhang, X., Rives, C., Brissova, M., Hughes, E., Baker, M., Powers, A.C., Kaufman, D.B., Shea, L.D., and Lowe, W.L.: Polymer scaffolds as synthetic microenvironments for extrahepatic islet transplantation. Transplantation 82, 452459 (2006).Google Scholar
64.Hlavaty, K.A., Gibly, R.F., Zhang, X., Rives, C.B., Graham, J.G., Lowe, W.L., Luo, X., and Shea, L.D.: Enhancing human islet transplantation by localized release of trophic factors from PLG scaffolds. Am. J. Transplant. 14, 15231532 (2014).Google Scholar
65.Graham, J.G., Zhang, X., Goodman, A., Pothoven, K., Houlihan, J., Wang, S., Gower, R.M., Luo, X., and Shea, L.D.: PLG scaffold delivered antigen-specific regulatory T cells induce systemic tolerance in autoimmune diabetes. Tissue Eng. A 19, 14651475 (2013).Google Scholar
66.Kheradmand, T., Wang, S., Gibly, R.F., Zhang, X., Holland, S., Tasch, J., Graham, J.G., Kaufman, D.B., Miller, S.D., Shea, L.D., and Luo, X.: Permanent protection of PLG scaffold transplanted allogeneic islet grafts in diabetic mice treated with ECDI-fixed donor splenocyte infusions. Biomaterials 32, 45174524 (2011).Google Scholar
67.Gibly, R.F., Zhang, X., Lowe, W.L., and Shea, L.D.: Porous scaffolds support extrahepatic human islet transplantation, engraftment, and function in mice. Cell Transplant. 22, 811819 (2013).Google Scholar
68.Salvay, D.M., Rives, C.B., Zhang, X., Chen, F., Kaufman, D.B., Lowe, W.L., and Shea, L.D.: Extracellular matrix protein-coated scaffolds promote the reversal of diabetes after extrahepatic islet transplantation. Transplantation 85, 14561464 (2008).Google Scholar
69.Pedraza, E., Brady, A.-C., Fraker, C.A., Molano, R.D., Sukert, S., Berman, D.M., Kenyon, N.S., Pileggi, A., Ricordi, C., and Stabler, C.L.: Macroporous three-dimensional PDMS scaffolds for extrahepatic islet transplantation. Cell Transplant. 22, 11231135 (2013).Google Scholar
70.Tuch, B.E., Gao, S.Y., and Lees, J.G.: Scaffolds for islets and stem cells differentiated into insulin-secreting cells. Front Biosci. (Landmark Ed). 19, 126138 (2014).Google Scholar
71.Berman, D.M., Molano, R.D., Fotino, C., Ulissi, U., Gimeno, J., Mendez, A.J., Kenyon, N.M., Kenyon, N.S., Andrews, D.M., Ricordi, C., and Pileggi, A.: Bioengineering the endocrine pancreas: intraomental islet transplantation within a biologic resorbable scaffold. Diabetes 65, 13501361 (2016).Google Scholar
72.Berman, D.M., O'Neil, J.J., Coffey, L.C.K., Chaffanjon, P.C.J., Kenyon, N.M., Ruiz, P., Pileggi, A., Ricordi, C., and Kenyon, N.S.: Long-term survival of nonhuman primate islets implanted in an omental pouch on a biodegradable scaffold. Am. J. Transplant. 9, 91104 (2009).Google Scholar
73.Weizman, A., Michael, I., Wiesel-Motiuk, N., Rezania, A., and Levenberg, S.: The effect of endothelial cells on hESC-derived pancreatic progenitors in a 3D environment. Biomater. Sci. 2, 17061714 (2014).Google Scholar
74.Mao, G.-H., Chen, G.-A., Bai, H.-Y., Song, T.-R., and Wang, Y.-X.: The reversal of hyperglycaemia in diabetic mice using PLGA scaffolds seeded with islet-like cells derived from human embryonic stem cells. Biomaterials 30, 17061714 (2009).Google Scholar
75.Shih, H.P., Wang, A., and Sander, M.: Pancreas organogenesis: from lineage determination to morphogenesis. Annu. Rev. Cell Dev. Biol. 29, 81105 (2013).Google Scholar
76.Broutier, L., Andersson-Rolf, A., Hindley, C.J., Boj, S.F., Clevers, H., Koo, B.-K., and Huch, M.: Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. Nat. Protoc. 11, 17241743 (2016).Google Scholar
77.Hindley, C.J., Cordero-Espinoza, L., and Huch, M.: Organoids from adult liver and pancreas: stem cell biology and biomedical utility. Dev. Biol. 420, 251261 (2016).Google Scholar
78.Hohwieler, M., Illing, A., Hermann, P.C., Mayer, T., Stockmann, M., Perkhofer, L., Eiseler, T., Antony, J.S., Müller, M., Renz, S., Kuo, C.-C., Lin, Q., Sendler, M., Breunig, M., Kleiderman, S.M., Lechel, A., Zenker, M., Leichsenring, M., Rosendahl, J., Zenke, M., Sainz, B., Mayerle, J., Costa, I.G., Seufferlein, T., Kormann, M., Wagner, M., Liebau, S., and Kleger, A.: Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling. Gut 66, 473486 (2017).Google Scholar
79.Ramachandran, S.D., Schirmer, K., Münst, B., Heinz, S., Ghafoory, S., Wölfl, S., Simon-Keller, K., Marx, A., Øie, C.I., Ebert, M.P., Walles, H., Braspenning, J., and Breitkopf-Heinlein, K.: In vitro generation of functional liver organoid-like structures using adult human cells. PLoS ONE 10, e0139345 (2015).Google Scholar
80.Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M.M.A., Ellis, E., van Wenum, M., Fuchs, S.A., de Ligt, J., van de Wetering, M., Sasaki, N., Boers, S.J., Kemperman, H., de Jonge, J., Ijzermans, J.N.M., Nieuwenhuis, E.E.S., Hoekstra, R., Strom, S., Vries, R.R.G., van der Laan, L.J.W., Cuppen, E., and Clevers, H.: Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160, 299312 (2015).Google Scholar
81.Takebe, T., Sekine, K., Enomura, M., Koike, H., Kimura, M., Ogaeri, T., Zhang, R.-R., Ueno, Y., Zheng, Y.-W., Koike, N., Aoyama, S., Adachi, Y., and Taniguchi, H.: Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499, 481484 (2013).Google Scholar
82.Cai, J., Zhao, Y., Liu, Y., Ye, F., Song, Z., Qin, H., Meng, S., Chen, Y., Zhou, R., Song, X., Guo, Y., Ding, M., and Deng, H.: Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology 45, 12291239 (2007).Google Scholar
83.Basma, H., Soto-Gutierrez, A., Yannam, G.R., Liu, L., Ito, R., Yamamoto, T., Ellis, E., Carson, S.D., Sato, S., Chen, Y., Muirhead, D., Navarro-Alvarez, N., Wong, R.J., Roy-Chowdhury, J., Platt, J.L., Mercer, D.F., Miller, J.D., Strom, S.C., Kobayashi, N., and Fox, I.J.: Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology 136, 990999 (2009).Google Scholar
84.Touboul, T., Hannan, N.R.F., Corbineau, S., Martinez, A., Martinet, C., Branchereau, S., Mainot, S., Strick-Marchand, H., Pedersen, R., Di Santo, J., Weber, A., and Vallier, L.: Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology 51, 17541765 (2010).Google Scholar
85.Park, Y., Chen, Y., Ordovas, L., and Verfaillie, C.M.: Hepatic differentiation of human embryonic stem cells on microcarriers. J. Biotechnol. 174, 3948 (2014).Google Scholar
86.Si-Tayeb, K., Lemaigre, F.P., and Duncan, S.A.: Organogenesis and development of the liver. Dev. Cell 18, 175189 (2010).Google Scholar
87.Duncan, A.W., Dorrell, C., and Grompe, M.: Stem cells and liver regeneration. Gastroenterology 137, 466481 (2009).Google Scholar
88.Davidson, M.D., Ware, B.R., and Khetani, S.R.: Stem cell-derived liver cells for drug testing and disease modeling. Discov. Med. 19, 349358 (2015).Google Scholar
89.Gissen, P. and Arias, I.M.: Structural and functional hepatocyte polarity and liver disease. J Hepatol 63, 10231037 (2015).Google Scholar
90.Si-Tayeb, K., Noto, F.K., Nagaoka, M., Li, J., Battle, M.A., Duris, C., North, P.E., Dalton, S., and Duncan, S.A.: Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51, 297305 (2010).Google Scholar
91.Mitaka, T.: The current status of primary hepatocyte culture. Int. J. Exp. Pathol. 79, 393409 (1998).Google Scholar
92.Stoller, J.K. and Aboussouan, L.S.: Alpha1-antitrypsin deficiency. Lancet 365, 22252236 (2005).Google Scholar
93.Skardal, A., Devarasetty, M., Rodman, C., Atala, A., and Soker, S.: Liver-tumor hybrid organoids for modeling tumor growth and drug response in vitro. Ann. Biomed. Eng. 43, 23612373 (2015).Google Scholar
94.McCracken, K.W., Catá, E.M., Crawford, C.M., Sinagoga, K.L., Schumacher, M., Rockich, B.E., Tsai, Y.-H., Mayhew, C.N., Spence, J.R., Zavros, Y., and Wells, J.M.: Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516, 400404 (2014).Google Scholar
95.Bartfeld, S., Bayram, T., van de Wetering, M., Huch, M., Begthel, H., Kujala, P., Vries, R., Peters, P.J., and Clevers, H.: In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148, 126136. (2015).Google Scholar
96.McCracken, K.W. and Wells, J.M.: Mechanisms of embryonic stomach development. Semin. Cell Dev. Biol. 66, 3642 (2017). doi: 10.1016/j.semcdb.2017.02.004.Google Scholar
97.Odze, R.D.: Barrett esophagus: histology and pathology for the clinician. Nature Reviews Gastroenterol. Hepatol. 6, 478490 (2009).Google Scholar
98.Lisovsky, M. and Srivastava, A.: Barrett esophagus. Surg. Pathol. Clin. 6, 475496 (2013).Google Scholar
99.DeWard, A.D., Cramer, J., and Lagasse, E.: Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep. 9, 701711 (2014).Google Scholar
100.Mou, H., Vinarsky, V., Tata, P.R., Brazauskas, K., Choi, S.H., Crooke, A.K., Zhang, B., Solomon, G.M., Turner, B., Bihler, H., Harrington, J., Lapey, A., Channick, C., Keyes, C., Freund, A., Artandi, S., Mense, M., Rowe, S., Engelhardt, J.F., Hsu, Y.-C., and Rajagopal, J.: Dual SMAD signaling inhibition enables long-term expansion of diverse epithelial basal cells. Cell Stem Cell 19, 217231 (2016).Google Scholar
101.Green, N., Huang, Q., Khan, L., Battaglia, G., Corfe, B., MacNeil, S., and Bury, J.P.: The development and characterization of an organotypic tissue-engineered human esophageal mucosal model. Tissue Eng. A 16, 10531064 (2010).Google Scholar
102.Ogawa, M., Ogawa, S., Bear, C.E., Ahmadi, S., Chin, S., Li, B., Grompe, M., Keller, G., Kamath, B.M., and Ghanekar, A.: Directed differentiation of cholangiocytes from human pluripotent stem cells. Nat. Biotechnol. 33, 853861 (2015).Google Scholar
103.Zhao, D., Chen, S., Cai, J., Guo, Y., Song, Z., Che, J., Liu, C., Wu, C., Ding, M., and Deng, H.: Derivation and characterization of hepatic progenitor cells from human embryonic stem cells. PLoS ONE 4, e6468 (2009).Google Scholar
104.Dianat, N., Dubois-Pot-Schneider, H., Steichen, C., Desterke, C., Leclerc, P., Raveux, A., Combettes, L., Weber, A., Corlu, A., and Dubart-Kupperschmitt, A.: Generation of functional cholangiocyte-like cells from human pluripotent stem cells and HepaRG cells. Hepatology 60, 700714 (2014).Google Scholar
105.Sampaziotis, F., Cardoso de Brito, M., Madrigal, P., Bertero, A., Saeb-Parsy, K., Soares, F.A.C., Schrumpf, E., Melum, E., Karlsen, T.H., Bradley, J.A., Gelson, W.T.H., Davies, S., Baker, A., Kaser, A., Alexander, G.J., Hannan, N.R.F., and Vallier, L.: Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nat. Biotechnol. 33, 845852 (2015).Google Scholar
106.Hosey, C.M., Broccatelli, F., and Benet, L.Z.: Predicting when biliary excretion of parent drug is a major route of elimination in humans. AAPS J. 16, 10851096 (2014).Google Scholar
107.Sharifi, M. and Ghafourian, T.: Estimation of biliary excretion of foreign compounds using properties of molecular structure. AAPS J. 16, 6578 (2014).Google Scholar
108.Colombo, C., Battezzati, P.M., Strazzabosco, M., and Podda, M.: Liver and biliary problems in cystic fibrosis. Semin. Liver Dis. 18, 227235 (1998).Google Scholar
109.Cardinale, V., Wang, Y., Carpino, G., Mendel, G., Alpini, G., Gaudio, E., Reid, L.M., and Alvaro, D.: The biliary tree—a reservoir of multipotent stem cells. Nat. Rev. Gastroenterol. Hepatol. 9, 231240 (2012).Google Scholar
110.Tanimizu, N., Miyajima, A., and Mostov, K.E.: Liver progenitor cells develop cholangiocyte-type epithelial polarity in three-dimensional culture. Mol. Biol. Cell 18, 14721479 (2007).Google Scholar
111.Gordillo, M., Evans, T., and Gouon-Evans, V.: Orchestrating liver development. Development 142, 20942108 (2015).Google Scholar
112.Rock, J.R., Onaitis, M.W., Rawlins, E.L., Lu, Y., Clark, C.P., Xue, Y., Randell, S.H., and Hogan, B.L.M.: Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc. Natl. Acad. Sci. USA 106, 1277112775 (2009).Google Scholar
113.Rock, J.R., Randell, S.H., and Hogan, B.L.M.: Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. Dis. Model. Mech. 3, 545556 (2010).Google Scholar
114.Hackett, T.-L., Shaheen, F., Johnson, A., Wadsworth, S., Pechkovsky, D.V., Jacoby, D.B., Kicic, A., Stick, S.M., and Knight, D.A.: Characterization of side population cells from human airway epithelium. Stem Cells 26, 25762585 (2008).Google Scholar
115.Hong, K.U., Reynolds, S.D., Watkins, S., Fuchs, E., and Stripp, B.R.: Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium. AJPA 164, 577588 (2004).Google Scholar
116.Boers, J.E., Ambergen, A.W., and Thunnissen, F.B.: Number and proliferation of basal and parabasal cells in normal human airway epithelium. Am. J. Respir. Crit. Care Med. 157(Pt 1), 20002006 (1998).Google Scholar
117.Pardo-Saganta, A., Law, B.M., Tata, P.R., Villoria, J., Saez, B., Mou, H., Zhao, R., and Rajagopal, J.: Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations. Cell Stem Cell 16, 184197 (2015).Google Scholar
118.Chen, Y.-W., Huang, S.X., de Carvalho, A.L.R.T., Ho, S.-H., Islam, M.N., Volpi, S., Notarangelo, L.D., Ciancanelli, M., Casanova, J.-L., Bhattacharya, J., Liang, A.F., Palermo, L.M., Porotto, M., Moscona, A., and Snoeck, H.-W.: A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat. Cell Biol. 372, 3 (2017).Google Scholar
119.Butler, C.R., Hynds, R.E., Gowers, K.H.C., Lee, D.D.H., Brown, J.M., Crowley, C., Teixeira, V.H., Smith, C.M., Urbani, L., Hamilton, N.J., Thakrar, R.M., Booth, H.L., Birchall, M.A., De Coppi, P., Giangreco, A., O'Callaghan, C., and Janes, S.M.: Rapid expansion of human epithelial stem cells suitable for airway tissue engineering. Am. J. Respir. Crit. Care Med. 194, 156168 (2016).Google Scholar
120.Danahay, H., Pessotti, A.D., Coote, J., Montgomery, B.E., Xia, D., Wilson, A., Yang, H., Wang, Z., Bevan, L., Thomas, C., Petit, S., London, A., LeMotte, P., Doelemeyer, A., Vélez-Reyes, G.L., Bernasconi, P., Fryer, C.J., Edwards, M., Capodieci, P., Chen, A., Hild, M., and Jaffe, A.B.: Notch2 is required for inflammatory cytokine-driven goblet cell metaplasia in the lung. Cell Rep. 10, 239252 (2015).Google Scholar
121.Hild, M. and Jaffe, A.B.: Production of 3-D Airway Organoids From Primary Human Airway Basal Cells and Their Use in High-Throughput Screening (John Wiley & Sons, Inc., Hoboken, NJ, USA, 2007).Google Scholar
122.Kumar, M., Jordan, N., Melton, D., and Grapin-Botton, A.: Signals from lateral plate mesoderm instruct endoderm toward a pancreatic fate. Dev. Biol. 259, 109122 (2003).Google Scholar
123.Chu, H.W., Rios, C., Huang, C., Wesolowska-Andersen, A., Burchard, E.G., O'Connor, B.P., Fingerlin, T.E., Nichols, D., Reynolds, S.D., and Seibold, M.A.: CRISPR–Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18. Gene Ther. 22, 822829 (2015).Google Scholar
124.Gao, X., Bali, A.S., Randell, S.H., and Hogan, B.L.M.: GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells. J. Cell Biol. 211, 669682 (2015).Google Scholar
125.Barkauskas, C.E., Chung, M.-I., Fioret, B., Gao, X., Katsura, H., and Hogan, B.L.M.: Lung organoids: current uses and future promise. Development 144, 986997 (2017).Google Scholar
126.Konishi, S., Gotoh, S., Tateishi, K., Yamamoto, Y., Korogi, Y., Nagasaki, T., Matsumoto, H., Muro, S., Hirai, T., Ito, I., Tsukita, S., and Mishima, M.: Directed induction of functional multi-ciliated cells in proximal airway epithelial spheroids from human pluripotent stem cells. Stem Cell Rep. 6, 1825 (2016).Google Scholar
127.Gotoh, S., Ito, I., Nagasaki, T., Yamamoto, Y., Konishi, S., Korogi, Y., Matsumoto, H., Muro, S., Hirai, T., Funato, M., Mae, S.-I., Toyoda, T., Sato-Otsubo, A., Ogawa, S., Osafune, K., and Mishima, M.: Generation of alveolar epithelial spheroids via isolated progenitor cells from human pluripotent stem cells. Stem Cell Rep. 3, 394403 (2014).Google Scholar
128.Dye, B.R., Hill, D.R., Ferguson, M.A., Tsai, Y.-H., Nagy, M.S., Dyal, R., Wells, J.M., Mayhew, C.N., Nattiv, R., Klein, O.D., White, E.S., Deutsch, G.H., and Spence, J.R.: In vitro generation of human pluripotent stem cell derived lung organoids. Elife 4, e05098 (2015).Google Scholar
129.Dye, B.R., Dedhia, P.H., Miller, A.J., Nagy, M.S., White, E.S., Shea, L.D., and Spence, J.R.: A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. Elife 5, 3025 (2016).Google Scholar
130.Barkauskas, C.E., Cronce, M.J., Rackley, C.R., Bowie, E.J., Keene, D.R., Stripp, B.R., Randell, S.H., Noble, P.W., and Hogan, B.L.M.: Type 2 alveolar cells are stem cells in adult lung. J. Clin. Invest. 123, 30253036 (2013).Google Scholar
131.Lee, J.-H., Bhang, D.H., Beede, A., Huang, T.L., Stripp, B.R., Bloch, K.D., Wagers, A.J., Tseng, Y.-H., Ryeom, S., and Kim, C.F.: Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell 156, 440455 (2014).Google Scholar
132.Booth, A.J., Hadley, R., Cornett, A.M., Dreffs, A.A., Matthes, S.A., Tsui, J.L., Weiss, K., Horowitz, J.C., Fiore, V.F., Barker, T.H., Moore, B.B., Martinez, F.J., Niklason, L.E., and White, E.S.: Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am. J. Respir. Crit. Care Med. 186, 866876 (2012).Google Scholar
133.Liu, J.M.H., Zhang, J., Zhang, X., Hlavaty, K.A., Ricci, C.F., Leonard, J.N., Shea, L.D., and Gower, R.M.: Transforming growth factor-beta 1 delivery from microporous scaffolds decreases inflammation post-implant and enhances function of transplanted islets. Biomaterials 80, 1119 (2016).Google Scholar
134.Margul, D.J., Park, J., Boehler, R.M., Smith, D.R., Johnson, M.A., McCreedy, D.A., He, T., Ataliwala, A., Kukushliev, T.V., Liang, J., Sohrabi, A., Goodman, A.G., Walthers, C.M., Shea, L.D., and Seidlits, S.K.: Reducing neuroinflammation by delivery of IL-10 encoding lentivirus from multiple-channel bridges. Bioeng. Transl. Med. 1, 136148 (2016).Google Scholar