SpringerLink
Log in

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

  • Biomaterials for 3D Cell Biology Prospective Article
  • Published:
MRS Communications Aims and scope Submit manuscript

Abstract

Human organoid models recapitulate many aspects of the complex composition and function of native organs. One of the main challenges in develo** 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Table I
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. A.J. Miller and J.R. Spence: In vitro models to study human lung development, disease and homeostasis. Physiology (Bethesda) 32, 246–260 (2017).

    CAS  Google Scholar 

  2. M. Aurora and J.R. Spence: hPSC-derived lung and intestinal organoids as models of human fetal tissue. Dev. Biol. 420, 230–238 (2016).

    Article  CAS  Google Scholar 

  3. G.-A. Kim, J.R. Spence, and S. Takayama: Bioengineering for intestinal organoid cultures. Curr. Opin. Biotechnol. 47, 51–58 (2017).

    Article  CAS  Google Scholar 

  4. B.R. Dye, A.J. Miller, and J.R. Spence: How to grow a lung: applying principles of developmental biology to generate lung lineages from human pluripotent stem cells. Curr. Pathobiol. Rep. 4, 47–57 (2016).

    Article  Google Scholar 

  5. H. Clevers: Modeling development and disease with organoids. Cell 165, 1586–1597 (2016).

    Article  CAS  Google Scholar 

  6. S. Bartfeld and H. Clevers: Stem cell-derived organoids and their application for medical research and patient treatment. J. Mol. Med. 95, 729–738 (2017).

    Article  CAS  Google Scholar 

  7. J. Drost and H. Clevers: Translational applications of adult stem cell-derived organoids. Development 144, 968–975 (2017).

    Article  CAS  Google Scholar 

  8. P.H. Dedhia, N. Bertaux-Skeirik, Y. Zavros, and J.R. Spence: Organoid models of human gastrointestinal development and disease. Gastroenterology 150, 1098–1112 (2016).

    Article  Google Scholar 

  9. A. Fatehullah, S.H. Tan, and N. Barker: Organoids as an in vitro model of human development and disease. Nat. Cell Biol. 18, 246–254 (2016).

    Article  Google Scholar 

  10. J.Z. Johnson and D. Hockemeyer: Human stem cell-based disease modeling: prospects and challenges. Curr. Opin. Cell Biol. 37, 84–90 (2015).

    Article  CAS  Google Scholar 

  11. M. Huch and B.-K. Koo: Modeling mouse and human development using organoid cultures. Development 142, 3113–3125 (2015).

    Article  CAS  Google Scholar 

  12. M.B. Rookmaaker, F. Schutgens, M.C. Verhaar, and H. Clevers: Development and application of human adult stem or progenitor cell organoids. Nat. Rev. Nephrol. 11, 546–554 (2015).

    Article  CAS  Google Scholar 

  13. E.R. Shamir and A.J. Ewald: Three-dimensional organotypic culture: experimental models of mammalian biology and disease. Nat. Rev. Mol. Cell Biol. 15, 647–664 (2014).

    Article  CAS  Google Scholar 

  14. T. Sato, D.E. Stange, M. Ferrante, R.G.J. Vries, J.H. van Es, S. Van den Brink, W.J. Van Houdt, A. Pronk, J. Van Gorp, P.D. Siersema, and H. Clevers: Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 141, 1762–1772 (2011).

    Article  CAS  Google Scholar 

  15. T. Sato and H. Clevers: Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340, 1190–1194 (2013).

    Article  CAS  Google Scholar 

  16. M.M. Mahe, N. Sundaram, C.L. Watson, N.F. Shroyer, and M.A. Helmrath: Establishment of human epithelial enteroids and colonoids from whole tissue and biopsy. J. Vis. Exp. (97) (2015).

    Google Scholar 

  17. Z. Jabaji, G.J. Brinkley, H.A. Khalil, C.M. Sears, N.Y. Lei, M. Lewis, M. Stelzner, M.G. Martin, and J.C.Y. Dunn: Type I collagen as an extracellular matrix for the in vitro growth of human small intestinal epithelium. PLoS ONE 9, e107814 (2014).

    Article  Google Scholar 

  18. N. Gjorevski, N. Sachs, A. Manfrin, S. Giger, M.E. Bragina, P. Ordóñez-Morán, H. Clevers, and M.P. Lutolf: Designer matrices for intestinal stem cell and organoid culture. Nature 539, 560–564 (2016).

    Article  CAS  Google Scholar 

  19. J.R. Spence, C.N. Mayhew, S.A. Rankin, M.F. Kuhar, J.E. Vallance, K. Tolle, E.E. Hoskins, V.V. Kalinichenko, S.I. Wells, A.M. Zorn, N.F. Shroyer, and J.M. Wells: Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470, 105–109 (2011).

    Article  Google Scholar 

  20. J.M. Wells and J.R. Spence: How to make an intestine. Development 141, 752–760 (2014).

    Article  CAS  Google Scholar 

  21. S.R. Finkbeiner, J.J. Freeman, M.M. Wieck, W. El-Nachef, C.H. Altheim, Y.-H. Tsai, S. Huang, R. Dyal, E.S. White, T.C. Grikscheit, D.H. Teitelbaum, and J.R. Spence: Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoids. Biol. Open 4, 1462–1472 (2015).

    Article  CAS  Google Scholar 

  22. C.L. Watson, M.M. Mahe, J. Múnera, J.C. Howell, N. Sundaram, H.M. Poling, J.I. Schweitzer, J.E. Vallance, C.N. Mayhew, Y. Sun, G. Grabowski, S.R. Finkbeiner, J.R. Spence, N.F. Shroyer, J.M. Wells, and M.A. Helmrath: An in vivo model of human small intestine using pluripotent stem cells. Nat. Med. 20, 1310–1314 (2014).

    Article  CAS  Google Scholar 

  23. S.R. Finkbeiner, X.-L. Zeng, B. Utama, R.L. Atmar, N.F. Shroyer, and M.K. Estes: Stem cell-derived human intestinal organoids as an infection model for rotaviruses. mBio 3, e00159–12 (2012).

    Article  CAS  Google Scholar 

  24. J.L. Leslie, S. Huang, J.S. Opp, M.S. Nagy, M. Kobayashi, V.B. Young, and J.R. Spence: Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function. Infect. Immun. 83, 138–145 (2015).

    Article  Google Scholar 

  25. O. Kovbasnjuk, N.C. Zachos, J. In, J. Foulke-Abel, K. Ettayebi, J.M. Hyser, J.R. Broughman, X.-L. Zeng, S. Middendorp, H.R. de Jonge, M.K. Estes, and M. Donowitz: Human enteroids: preclinical models of non-inflammatory diarrhea. Stem Cell Res. Ther. 4(Suppl. 1), S3 (2013).

    Article  Google Scholar 

  26. M. Fujii, M. Shimokawa, S. Date, A. Takano, M. Matano, K. Nanki, Y. Ohta, K. Toshimitsu, Y. Nakazato, K. Kawasaki, T. Uraoka, T. Watanabe, T. Kanai, and T. Sato: A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 18, 827–838 (2016).

    Article  CAS  Google Scholar 

  27. A. Cristobal, H.W.P. van den Toorn, M. van de Wetering, H. Clevers, A.J.R. Heck, and S. Mohammed: Personalized proteome profiles of healthy and tumor human colon organoids reveal both individual diversity and basic features of colorectal cancer. Cell Rep. 18, 263–274 (2017).

    Article  CAS  Google Scholar 

  28. M. Matano, S. Date, M. Shimokawa, A. Takano, M. Fujii, Y. Ohta, T. Watanabe, T. Kanai, and T. Sato: Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat. Med. 21, 256–262 (2015).

    Article  CAS  Google Scholar 

  29. J. Drost, R.H. van Jaarsveld, B. Ponsioen, C. Zimberlin, R. van Boxtel, A. Buijs, N. Sachs, R.M. Overmeer, G.J. Offerhaus, H. Begthel, J. Korving, M. van de Wetering, G. Schwank, M. Logtenberg, E. Cuppen, H.J. Snippert, J.P. Medema, G.J.P.L. Kops, and H. Clevers: Sequential cancer mutations in cultured human intestinal stem cells. Nature 521, 43–47 (2015).

    Article  CAS  Google Scholar 

  30. A. Fumagalli, J. Drost, S.J.E. Suijkerbuijk, R. van Boxtel, J. de Ligt, G.J. Offerhaus, H. Begthel, E. Beerling, E.H. Tan, O.J. Sansom, E. Cuppen, H. Clevers, and J. van Rheenen: Genetic dissection of colorectal cancer progression by orthotopic transplantation of engineered cancer organoids. Proc. Natl. Acad. Sci. USA 114, E2357–E2364 (2017).

    Article  CAS  Google Scholar 

  31. M. Shimokawa, Y. Ohta, S. Nishikori, M. Matano, A. Takano, M. Fujii, S. Date, S. Sugimoto, T. Kanai, and T. Sato: Visualization and targeting of LGR5(+) human colon cancer stem cells. Nature 545, 187–192 (2017).

    Article  CAS  Google Scholar 

  32. T. Mizutani, Y. Tsukamoto, and H. Clevers: Oncogene-inducible organoids as a miniature platform to assess cancer characteristics. J. Cell Biol. 216, 1505–1507 (2017).

    Article  CAS  Google Scholar 

  33. P. Jung, T. Sato, A. Merlos-Suárez, F.M. Barriga, M. Iglesias, D. Rossell, H. Auer, M. Gallardo, M.A. Blasco, E. Sancho, H. Clevers, and E. Batlle: Isolation and in vitro expansion of human colonic stem cells. Nat. Med. 17, 1225–1227 (2011).

    Article  CAS  Google Scholar 

  34. J.F. Dekkers, G. Berkers, E. Kruisselbrink, A. Vonk, H.R. de Jonge, H.M. Janssens, I. Bronsveld, E.A. van de Graaf, E.E.S. Nieuwenhuis, R.H.J. Houwen, F.P. Vleggaar, J.C. Escher, Y.B. de Rijke, C.J. Majoor, H.G.M. Heijerman, K.M. de Winter-de Groot, H. Clevers, C.K. van der Ent, and J.M. Beekman: Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis. Sci. Transl. Med. 8, 344ra84–344ra84 (2016).

    Article  Google Scholar 

  35. L.A.W. Vijftigschild, G. Berkers, J.F. Dekkers, D.D. Zomer-van Ommen, E. Matthes, E. Kruisselbrink, A. Vonk, C.E. Hensen, S. Heida-Michel, M. Geerdink, H.M. Janssens, E.A. van de Graaf, I. Bronsveld, K.M. de Winter-de Groot, C.J. Majoor, H.G.M. Heijerman, H.R. de Jonge, J.W. Hanrahan, C.K. van der Ent, and J.M. Beekman: β2-Adrenergic receptor agonists activate CFTR in intestinal organoids and subjects with cystic fibrosis. Eur. Respir. J. 48, 768–779 (2016).

    Article  CAS  Google Scholar 

  36. M. van de Wetering, H.E. Francies, J.M. Francis, G. Bounova, F. Iorio, A. Pronk, W. van Houdt, J. Van Gorp, A. Taylor-Weiner, L. Kester, A. McLaren-Douglas, J. Blokker, S. Jaksani, S. Bartfeld, R. Volckman, P. van Sluis, V.S.W. Li, S. Seepo, C. Sekhar Pedamallu, K. Cibulskis, S.L. Carter, A. McKenna, M.S. Lawrence, L. Lichtenstein, C. Stewart, J. Koster, R. Versteeg, A. van Oudenaarden, J. Saez-Rodriguez, R.G.J. Vries, G. Getz, L. Wessels, M.R. Stratton, U. McDermott, M. Meyerson, M.J. Garnett, and H. Clevers: Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161, 933–945 (2015).

    Article  Google Scholar 

  37. M. Czerwinski and J.R. Spence: Hacking the matrix. Cell Stem Cell 20, 9–10 (2017).

    Article  CAS  Google Scholar 

  38. C.S. Hughes, L.M. Postovit, and G.A. Lajoie: Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10, 1886–1890 (2010).

    Article  CAS  Google Scholar 

  39. S.R. Finkbeiner and J.R. Spence: A gutsy task: generating intestinal tissue from human pluripotent stem cells. Dig. Dis. Sci. 58, 1176–1184 (2013).

    Article  Google Scholar 

  40. S.R. Finkbeiner, D.R. Hill, C.H. Altheim, P.H. Dedhia, M.J. Taylor, Y.-H. Tsai, A.M. Chin, M.M. Mahe, C.L. Watson, J.J. Freeman, R. Nattiv, M. Thomson, O.D. Klein, N.F. Shroyer, M.A. Helmrath, D.H. Teitelbaum, P.J. Dempsey, and J.R. Spence: Transcriptome-wide analysis reveals hallmarks of human intestine development and maturation in vitro and in vivo. Stem Cell Rep. 4, 1140–1155 (2015).

    Article  CAS  Google Scholar 

  41. Y.-H. Tsai, R. Nattiv, P.H. Dedhia, M.S. Nagy, A.M. Chin, M. Thomson, O.D. Klein, and J.R. Spence: In vitro patterning of pluripotent stem cell-derived intestine recapitulates in vivo human development. Development 144, 1045–1055 (2017).

    CAS  Google Scholar 

  42. M. Mojibian, M.M. Glavas, and T.J. Kieffer: Engineering the gut for insulin replacement to treat diabetes. J. Diab. Investig. 7(Suppl. 1), 87–93 (2016).

    Article  Google Scholar 

  43. D.A. Melton: Applied developmental biology: making human pancreatic beta cells for diabetics. Curr. Top. Dev. Biol. 117, 65–73 (2016).

    Article  Google Scholar 

  44. N. Quiskamp, J.E. Bruin, and T.J. Kieffer: Differentiation of human pluripotent stem cells into β-cells: potential and challenges. Best Pract. Res. Clin. Endocrinol. Metab. 29, 833–847 (2015).

    Article  CAS  Google Scholar 

  45. L.S.W. Loo, H.H. Lau, J.B. Jasmen, C.S. Lim, and A.K.K. Teo: An arduous journey from human pluripotent stem cells to functional pancreatic β cells. Diab. Obes. Metab. 355, 1318 (2017).

    Google Scholar 

  46. P.E. Cryer: The barrier of hypoglycemia in diabetes. Diabetes 57, 3169–3176 (2008).

    Article  CAS  Google Scholar 

  47. G. Pambianco, T. Costacou, D. Ellis, D.J. Becker, R. Klein, and T.J. Orchard: The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience. Diabetes 55, 1463–1469 (2006).

    Article  CAS  Google Scholar 

  48. F.B. Barton, M.R. Rickels, R. Alejandro, B.J. Hering, S. Wease, B. Naziruddin, J. Oberholzer, J.S. Odorico, M.R. Garfinkel, M. Levy, F. Pattou, T. Berney, A. Secchi, S. Messinger, P.A. Senior, P. Maffi, A. Posselt, P.G. Stock, D.B. Kaufman, X. Luo, F. Kandeel, E. Cagliero, N.A. Turgeon, P. Witkowski, A. Naji, P.J. O’Connell, C. Greenbaum, Y.C. Kudva, K.L. Brayman, M.J. Aull, C. Larsen, T.W.H. Kay, L.A. Fernandez, M.-C. Vantyghem, M. Bellin, and A.M.J. Shapiro: Improvement in outcomes of clinical islet transplantation: 1999–2010. Diab. Care 35, 1436–1445 (2012).

    Article  CAS  Google Scholar 

  49. T. Desai and L.D. Shea: Advances in islet encapsulation technologies. Nat. Rev. Drug Discov. 54, 2060 (2016).

    Google Scholar 

  50. R.P. Robertson: Islet transplantation a decade later and strategies for filling a half-full glass. Diabetes 59, 1285–1291 (2010).

    Article  CAS  Google Scholar 

  51. N.S. Kenyon, M. Chatzipetrou, M. Masetti, A. Ranuncoli, M. Oliveira, J.L. Wagner, A.D. Kirk, D.M. Harlan, L.C. Burkly, and C. Ricordi: Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proc. Natl. Acad. Sci. USA 96, 8132–8137 (1999).

    Article  CAS  Google Scholar 

  52. P. Srinivasan, G.C. Huang, S.A. Amiel, and N.D. Heaton: Islet cell transplantation. Postgrad. Med. J. 83, 224–229 (2007).

    Article  CAS  Google Scholar 

  53. F.W. Pagliuca, J.R. Millman, M. Gürtler, M. Segel, A. Van Dervort, J.H. Ryu, Q.P. Peterson, D. Greiner, and D.A. Melton: Generation of functional human pancreatic β cells in vitro. Cell 159, 428–439 (2014).

    Article  CAS  Google Scholar 

  54. F.W. Pagliuca, D.A. Melton: How to make a functional β-cell. Development 140, 2472–2483 (2013).

    Article  CAS  Google Scholar 

  55. A. Rezania, J.E. Bruin, P. Arora, A. Rubin, I. Batushansky, A. Asadi, S. O’Dwyer, N. Quiskamp, M. Mojibian, T. Albrecht, Y.H.C. Yang, J.D. Johnson, and T.J. Kieffer: Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat. Biotechnol. 32, 1121–1133 (2014).

    Article  CAS  Google Scholar 

  56. A. Rezania, J.E. Bruin, M.J. Riedel, M. Mojibian, A. Asadi, J. Xu, R. Gauvin, K. Narayan, F. Karanu, J.J. O’Neil, Z. Ao, G.L. Warnock, and T.J. Kieffer: Maturation of human embryonic stem cell-derived pancreatic progenitors into functional islets capable of treating pre-existing diabetes in mice. Diabetes 61, 2016–2029 (2012).

    Article  CAS  Google Scholar 

  57. A.J. Vegas, O. Veiseh, M. Gürtler, J.R. Millman, F.W. Pagliuca, A.R. Bader, J.C. Doloff, J. Li, M. Chen, K. Olejnik, H.H. Tam, S. Jhunjhunwala, E. Langan, S. Aresta-Dasilva, S. Gandham, J.J. McGarrigle, M.A. Bochenek, J. Hollister-Lock, J. Oberholzer, D.L. Greiner, G.C. Weir, D.A. Melton, R. Langer, and D.G. Anderson: Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat. Med. 22, 306–311 (2016).

    Article  CAS  Google Scholar 

  58. J.R. Millman, C. **e, A. Van Dervort, M. Gürtler, F.W. Pagliuca, and D.A. Melton: Corrigendum: generation of stem cell-derived β-cells from patients with type 1 diabetes. Nat. Commun. 7, 12379 (2016).

    Article  CAS  Google Scholar 

  59. T.C. Schulz, H.Y. Young, A.D. Agulnick, M.J. Babin, E.E. Baetge, A.G. Bang, A. Bhoumik, I. Cepa, R.M. Cesario, C. Haakmeester, K. Kadoya, J.R. Kelly, J. Kerr, L.A. Martinson, A.B. McLean, M.A. Moorman, J.K. Payne, M. Richardson, K.G. Ross, E.S. Sherrer, X. Song, A.Z. Wilson, E.P. Brandon, C.E. Green, E.J. Kroon, O.G. Kelly, K.A. D’Amour, and A.J. Robins: A scalable system for production of functional pancreatic progenitors from human embryonic stem cells. PLoS ONE 7, e37004 (2012).

    Article  CAS  Google Scholar 

  60. Y. Kim, H. Kim, U.H. Ko, Y. Oh, A. Lim, J.-W. Sohn, J.H. Shin, H. Kim, and Y.-M. Han: 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).

    Article  CAS  Google Scholar 

  61. D. Bosco, M. Armanet, P. Morel, N. Niclauss, A. Sgroi, Y.D. Muller, L. Giovannoni, G. Parnaud, and T. Berney: Unique arrangement of alpha- and beta-cells in human islets of Langerhans. Diabetes 59, 1202–1210 (2010).

    Article  CAS  Google Scholar 

  62. R.F. Gibly, X. Zhang, M.L. Graham, B.J. Hering, D.B. Kaufman, W.L. Lowe, and L.D. Shea: Extrahepatic islet transplantation with microporous polymer scaffolds in syngeneic mouse and allogeneic porcine models. Biomaterials 32, 9677–9684 (2011).

    Article  CAS  Google Scholar 

  63. H. Blomeier, X. Zhang, C. Rives, M. Brissova, E. Hughes, M. Baker, A.C. Powers, D.B. Kaufman, L.D. Shea, and W.L. Lowe: Polymer scaffolds as synthetic microenvironments for extrahepatic islet transplantation. Transplantation 82, 452–459 (2006).

    Article  CAS  Google Scholar 

  64. K.A. Hlavaty, R.F. Gibly, X. Zhang, C.B. Rives, J.G. Graham, W.L. Lowe, X. Luo, and L.D. Shea: Enhancing human islet transplantation by localized release of trophic factors from PLG scaffolds. Am. J. Transplant. 14, 1523–1532 (2014).

    Article  CAS  Google Scholar 

  65. J.G. Graham, X. Zhang, A. Goodman, K. Pothoven, J. Houlihan, S. Wang, R.M. Gower, X. Luo, and L.D. Shea: PLG scaffold delivered antigen-specific regulatory T cells induce systemic tolerance in autoimmune diabetes. Tissue Eng. A 19, 1465–1475 (2013).

    Article  CAS  Google Scholar 

  66. T. Kheradmand, S. Wang, R.F. Gibly, X. Zhang, S. Holland, J. Tasch, J.G. Graham, D.B. Kaufman, S.D. Miller, L.D. Shea, and X. Luo: Permanent protection of PLG scaffold transplanted allogeneic islet grafts in diabetic mice treated with ECDI-fixed donor splenocyte infusions. Biomaterials 32, 4517–4524 (2011).

    Article  CAS  Google Scholar 

  67. R.F. Gibly, X. Zhang, W.L. Lowe, and L.D. Shea: Porous scaffolds support extrahepatic human islet transplantation, engraftment, and function in mice. Cell Transplant. 22, 811–819 (2013).

    Article  Google Scholar 

  68. D.M. Salvay, C.B. Rives, X. Zhang, F. Chen, D.B. Kaufman, W.L. Lowe, and L.D. Shea: Extracellular matrix protein-coated scaffolds promote the reversal of diabetes after extrahepatic islet transplantation. Transplantation 85, 1456–1464 (2008).

    Article  CAS  Google Scholar 

  69. E. Pedraza, A.-C. Brady, C.A. Fraker, R.D. Molano, S. Sukert, D.M. Berman, N.S. Kenyon, A. Pileggi, C. Ricordi, and C.L. Stabler: Macroporous three-dimensional PDMS scaffolds for extrahepatic islet transplantation. Cell Transplant. 22, 1123–1135 (2013).

    Article  Google Scholar 

  70. B.E. Tuch, S.Y. Gao, and J.G. Lees: Scaffolds for islets and stem cells differentiated into insulin-secreting cells. Front Biosci. (Landmark Ed). 19, 126–138 (2014).

    CAS  Google Scholar 

  71. D.M. Berman, R.D. Molano, C. Fotino, U. Ulissi, J. Gimeno, A.J. Mendez, N.M. Kenyon, N.S. Kenyon, D.M. Andrews, C. Ricordi, and A. Pileggi: Bioengineering the endocrine pancreas: intraomental islet transplantation within a biologic resorbable scaffold. Diabetes 65, 1350–1361 (2016).

    Article  CAS  Google Scholar 

  72. D.M. Berman, J.J. O’Neil, L.C.K. Coffey, P.C.J. Chaffanjon, N.M. Kenyon, P. Ruiz, A. Pileggi, C. Ricordi, and N.S. Kenyon: Long-term survival of nonhuman primate islets implanted in an omental pouch on a biodegradable scaffold. Am. J. Transplant. 9, 91–104 (2009).

    Article  CAS  Google Scholar 

  73. A. Weizman, I. Michael, N. Wiesel-Motiuk, A. Rezania, and S. Levenberg: The effect of endothelial cells on hESC-derived pancreatic progenitors in a 3D environment. Biomater. Sci. 2, 1706–1714 (2014).

    Article  CAS  Google Scholar 

  74. G.-H. Mao, G.-A. Chen, H.-Y. Bai, T.-R. Song, and Y.-X. Wang: The reversal of hyperglycaemia in diabetic mice using PLGA scaffolds seeded with islet-like cells derived from human embryonic stem cells. Biomaterials 30, 1706–1714 (2009).

    Article  CAS  Google Scholar 

  75. H.P. Shih, A. Wang, and M. Sander: Pancreas organogenesis: from lineage determination to morphogenesis. Annu. Rev. Cell Dev. Biol. 29, 81–105 (2013).

    Article  CAS  Google Scholar 

  76. L. Broutier, A. Andersson-Rolf, C.J. Hindley, S.F. Boj, H. Clevers, B.-K. Koo, and M. Huch: Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. Nat. Protoc. 11, 1724–1743 (2016).

    Article  CAS  Google Scholar 

  77. C.J. Hindley, L. Cordero-Espinoza, and M. Huch: Organoids from adult liver and pancreas: stem cell biology and biomedical utility. Dev. Biol. 420, 251–261 (2016).

    Article  CAS  Google Scholar 

  78. M. Hohwieler, A. Illing, P.C. Hermann, T. Mayer, M. Stockmann, L. Perkhofer, T. Eiseler, J.S. Antony, M. Müller, S. Renz, C.-C. Kuo, Q. Lin, M. Sendler, M. Breunig, S.M. Kleiderman, A. Lechel, M. Zenker, M. Leichsenring, J. Rosendahl, M. Zenke, B. Sainz, J. Mayerle, I.G. Costa, T. Seufferlein, M. Kormann, M. Wagner, S. Liebau, and A. Kleger: Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling. Gut 66, 473–486 (2017).

    Article  CAS  Google Scholar 

  79. S.D. Ramachandran, K. Schirmer, B. Münst, S. Heinz, S. Ghafoory, S. Wölfl, K. Simon-Keller, A. Marx, C.I. Øie, M.P. Ebert, H. Walles, J. Braspenning, and K. Breitkopf-Heinlein: In vitro generation of functional liver organoid-like structures using adult human cells. PLoS ONE 10, e0139345 (2015).

    Article  Google Scholar 

  80. M. Huch, H. Gehart, R. van Boxtel, K. Hamer, F. Blokzijl, M.M.A. Verstegen, E. Ellis, M. van Wenum, S.A. Fuchs, J. de Ligt, M. van de Wetering, N. Sasaki, S.J. Boers, H. Kemperman, J. de Jonge, J.N.M. Ijzermans, E.E.S. Nieuwenhuis, R. Hoekstra, S. Strom, R.R.G. Vries, L.J.W. van der Laan, E. Cuppen, and H. Clevers: Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160, 299–312 (2015).

    Article  CAS  Google Scholar 

  81. T. Takebe, K. Sekine, M. Enomura, H. Koike, M. Kimura, T. Ogaeri, R.-R. Zhang, Y. Ueno, Y.-W. Zheng, N. Koike, S. Aoyama, Y. Adachi, and H. Taniguchi: Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499, 481–484 (2013).

    Article  CAS  Google Scholar 

  82. J. Cai, Y. Zhao, Y. Liu, F. Ye, Z. Song, H. Qin, S. Meng, Y. Chen, R. Zhou, X. Song, Y. Guo, M. Ding, and H. Deng: Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology 45, 1229–1239 (2007).

    Article  CAS  Google Scholar 

  83. H. Basma, A. Soto-Gutierrez, G.R. Yannam, L. Liu, R. Ito, T. Yamamoto, E. Ellis, S.D. Carson, S. Sato, Y. Chen, D. Muirhead, N. Navarro-Alvarez, R.J. Wong, J. Roy-Chowdhury, J.L. Platt, D.F. Mercer, J.D. Miller, S.C. Strom, N. Kobayashi, and I.J. Fox: Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology 136, 990–999 (2009).

    Article  CAS  Google Scholar 

  84. T. Touboul, N.R.F. Hannan, S. Corbineau, A. Martinez, C. Martinet, S. Branchereau, S. Mainot, H. Strick-Marchand, R. Pedersen, J. Di Santo, A. Weber, and L. Vallier: Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology 51, 1754–1765 (2010).

    Article  CAS  Google Scholar 

  85. Y. Park, Y. Chen, L. Ordovas, and C.M. Verfaillie: Hepatic differentiation of human embryonic stem cells on microcarriers. J. Biotechnol. 174, 39–48 (2014).

    Article  CAS  Google Scholar 

  86. K. Si-Tayeb, F.P. Lemaigre, and S.A. Duncan: Organogenesis and development of the liver. Dev. Cell 18, 175–189 (2010).

    Article  CAS  Google Scholar 

  87. A.W. Duncan, C. Dorrell, and M. Grompe: Stem cells and liver regeneration. Gastroenterology 137, 466–481 (2009).

    Article  Google Scholar 

  88. M.D. Davidson, B.R. Ware, and S.R. Khetani: Stem cell-derived liver cells for drug testing and disease modeling. Discov. Med. 19, 349–358 (2015).

    Google Scholar 

  89. P. Gissen and I.M. Arias: Structural and functional hepatocyte polarity and liver disease. J Hepatol 63, 1023–1037 (2015).

    Article  Google Scholar 

  90. K. Si-Tayeb, F.K. Noto, M. Nagaoka, J. Li, M.A. Battle, C. Duris, P.E. North, S. Dalton, and S.A. Duncan: Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51, 297–305 (2010).

    Article  CAS  Google Scholar 

  91. T. Mitaka: The current status of primary hepatocyte culture. Int. J. Exp. Pathol. 79, 393–409 (1998).

    Article  CAS  Google Scholar 

  92. J.K. Stoller and L.S. Aboussouan: Alpha1-antitrypsin deficiency. Lancet 365, 2225–2236 (2005).

    Article  CAS  Google Scholar 

  93. A. Skardal, M. Devarasetty, C. Rodman, A. Atala, and S. Soker: Liver-tumor hybrid organoids for modeling tumor growth and drug response in vitro. Ann. Biomed. Eng. 43, 2361–2373 (2015).

    Article  Google Scholar 

  94. K.W. McCracken, E.M. Catá, C.M. Crawford, K.L. Sinagoga, M. Schumacher, B.E. Rockich, Y.-H. Tsai, C.N. Mayhew, J.R. Spence, Y. Zavros, and J.M. Wells: Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516, 400–404 (2014).

    Article  CAS  Google Scholar 

  95. S. Bartfeld, T. Bayram, M. van de Wetering, M. Huch, H. Begthel, P. Kujala, R. Vries, P.J. Peters, and H. Clevers: In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148, 126–136. (2015).

    Article  Google Scholar 

  96. K.W. McCracken and J.M. Wells: Mechanisms of embryonic stomach development. Semin. Cell Dev. Biol. 66, 36–42 (2017). doi: 10.1016/j.semcdb.2017.02.004.

    Article  CAS  Google Scholar 

  97. R.D. Odze: Barrett esophagus: histology and pathology for the clinician. Nature Reviews Gastroenterol. Hepatol. 6, 478–490 (2009).

    Article  Google Scholar 

  98. M. Lisovsky and A. Srivastava: Barrett esophagus. Surg. Pathol. Clin. 6, 475–496 (2013).

    Article  Google Scholar 

  99. A.D. DeWard, J. Cramer, and E. Lagasse: Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep. 9, 701–711 (2014).

    Article  CAS  Google Scholar 

  100. H. Mou, V. Vinarsky, P.R. Tata, K. Brazauskas, S.H. Choi, A.K. Crooke, B. Zhang, G.M. Solomon, B. Turner, H. Bihler, J. Harrington, A. Lapey, C. Channick, C. Keyes, A. Freund, S. Artandi, M. Mense, S. Rowe, J.F. Engelhardt, Y.-C. Hsu, and J. Rajagopal: Dual SMAD signaling inhibition enables long-term expansion of diverse epithelial basal cells. Cell Stem Cell 19, 217–231 (2016).

    Article  CAS  Google Scholar 

  101. N. Green, Q. Huang, L. Khan, G. Battaglia, B. Corfe, S. MacNeil, and J.P. Bury: The development and characterization of an organotypic tissue-engineered human esophageal mucosal model. Tissue Eng. A 16, 1053–1064 (2010).

    Article  CAS  Google Scholar 

  102. M. Ogawa, S. Ogawa, C.E. Bear, S. Ahmadi, S. Chin, B. Li, M. Grompe, G. Keller, B.M. Kamath, and A. Ghanekar: Directed differentiation of cholangiocytes from human pluripotent stem cells. Nat. Biotechnol. 33, 853–861 (2015).

    Article  CAS  Google Scholar 

  103. D. Zhao, S. Chen, J. Cai, Y. Guo, Z. Song, J. Che, C. Liu, C. Wu, M. Ding, and H. Deng: Derivation and characterization of hepatic progenitor cells from human embryonic stem cells. PLoS ONE 4, e6468 (2009).

    Article  Google Scholar 

  104. N. Dianat, H. Dubois-Pot-Schneider, C. Steichen, C. Desterke, P. Leclerc, A. Raveux, L. Combettes, A. Weber, A. Corlu, and A. Dubart-Kupperschmitt: Generation of functional cholangiocyte-like cells from human pluripotent stem cells and HepaRG cells. Hepatology 60, 700–714 (2014).

    Article  CAS  Google Scholar 

  105. F. Sampaziotis, M. Cardoso de Brito, P. Madrigal, A. Bertero, K. Saeb-Parsy, F.A.C. Soares, E. Schrumpf, E. Melum, T.H. Karlsen, J.A. Bradley, W.T.H. Gelson, S. Davies, A. Baker, A. Kaser, G.J. Alexander, N.R.F. Hannan, and L. Vallier: Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nat. Biotechnol. 33, 845–852 (2015).

    Article  CAS  Google Scholar 

  106. C.M. Hosey, F. Broccatelli, and L.Z. Benet: Predicting when biliary excretion of parent drug is a major route of elimination in humans. AAPS J. 16, 1085–1096 (2014).

    Article  CAS  Google Scholar 

  107. M. Sharifi and T. Ghafourian: Estimation of biliary excretion of foreign compounds using properties of molecular structure. AAPS J. 16, 65–78 (2014).

    Article  CAS  Google Scholar 

  108. C. Colombo, P.M. Battezzati, M. Strazzabosco, and M. Podda: Liver and biliary problems in cystic fibrosis. Semin. Liver Dis. 18, 227–235 (1998).

    Article  CAS  Google Scholar 

  109. V. Cardinale, Y. Wang, G. Carpino, G. Mendel, G. Alpini, E. Gaudio, L.M. Reid, and D. Alvaro: The biliary tree—a reservoir of multipotent stem cells. Nat. Rev. Gastroenterol. Hepatol. 9, 231–240 (2012).

    Article  CAS  Google Scholar 

  110. N. Tanimizu, A. Miyajima, and K.E. Mostov: Liver progenitor cells develop cholangiocyte-type epithelial polarity in three-dimensional culture. Mol. Biol. Cell 18, 1472–1479 (2007).

    Article  CAS  Google Scholar 

  111. M. Gordillo, T. Evans, and V. Gouon-Evans: Orchestrating liver development. Development 142, 2094–2108 (2015).

    Article  CAS  Google Scholar 

  112. J.R. Rock, M.W. Onaitis, E.L. Rawlins, Y. Lu, C.P. Clark, Y. Xue, S.H. Randell, and B.L.M. Hogan: Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc. Natl. Acad. Sci. USA 106, 12771–12775 (2009).

    Article  CAS  Google Scholar 

  113. J.R. Rock, S.H. Randell, and B.L.M. Hogan: Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. Dis. Model. Mech. 3, 545–556 (2010).

    Article  CAS  Google Scholar 

  114. T.-L. Hackett, F. Shaheen, A. Johnson, S. Wadsworth, D.V. Pechkovsky, D.B. Jacoby, A. Kicic, S.M. Stick, and D.A. Knight: Characterization of side population cells from human airway epithelium. Stem Cells 26, 2576–2585 (2008).

    Article  Google Scholar 

  115. K.U. Hong, S.D. Reynolds, S. Watkins, E. Fuchs, and B.R. Stripp: Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium. AJPA 164, 577–588 (2004).

    CAS  Google Scholar 

  116. J.E. Boers, A.W. Ambergen, and F.B. Thunnissen: Number and proliferation of basal and parabasal cells in normal human airway epithelium. Am. J. Respir. Crit. Care Med. 157(Pt 1), 2000–2006 (1998).

    Article  CAS  Google Scholar 

  117. A. Pardo-Saganta, B.M. Law, P.R. Tata, J. Villoria, B. Saez, H. Mou, R. Zhao, and J. Rajagopal: Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations. Cell Stem Cell 16, 184–197 (2015).

    Article  CAS  Google Scholar 

  118. Y.-W. Chen, S.X. Huang, A.L.R.T. de Carvalho, S.-H. Ho, M.N. Islam, S. Volpi, L.D. Notarangelo, M. Ciancanelli, J.-L. Casanova, J. Bhattacharya, A.F. Liang, L.M. Palermo, M. Porotto, A. Moscona, and H.-W. Snoeck: A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat. Cell Biol. 372, 3 (2017).

    Google Scholar 

  119. C.R. Butler, R.E. Hynds, K.H.C. Gowers, D.D.H. Lee, J.M. Brown, C. Crowley, V.H. Teixeira, C.M. Smith, L. Urbani, N.J. Hamilton, R.M. Thakrar, H.L. Booth, M.A. Birchall, P. De Coppi, A. Giangreco, C. O’Callaghan, and S.M. Janes: Rapid expansion of human epithelial stem cells suitable for airway tissue engineering. Am. J. Respir. Crit. Care Med. 194, 156–168 (2016).

    Article  CAS  Google Scholar 

  120. H. Danahay, A.D. Pessotti, J. Coote, B.E. Montgomery, D. **a, A. Wilson, H. Yang, Z. Wang, L. Bevan, C. Thomas, S. Petit, A. London, P. LeMotte, A. Doelemeyer, G.L. Vélez-Reyes, P. Bernasconi, C.J. Fryer, M. Edwards, P. Capodieci, A. Chen, M. Hild, and A.B. Jaffe: Notch2 is required for inflammatory cytokine-driven goblet cell metaplasia in the lung. Cell Rep. 10, 239–252 (2015).

    Article  CAS  Google Scholar 

  121. M. Hild and A.B. Jaffe: 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. M. Kumar, N. Jordan, D. Melton, and A. Grapin-Botton: Signals from lateral plate mesoderm instruct endoderm toward a pancreatic fate. Dev. Biol. 259, 109–122 (2003).

    Article  CAS  Google Scholar 

  123. H.W. Chu, C. Rios, C. Huang, A. Wesolowska-Andersen, E.G. Burchard, B.P. O’Connor, T.E. Fingerlin, D. Nichols, S.D. Reynolds, and M.A. Seibold: CRISPR–Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18. Gene Ther. 22, 822–829 (2015).

    Article  CAS  Google Scholar 

  124. X. Gao, A.S. Bali, S.H. Randell, and B.L.M. Hogan: GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells. J. Cell Biol. 211, 669–682 (2015).

    Article  CAS  Google Scholar 

  125. C.E. Barkauskas, M.-I. Chung, B. Fioret, X. Gao, H. Katsura, and B.L.M. Hogan: Lung organoids: current uses and future promise. Development 144, 986–997 (2017).

    Article  CAS  Google Scholar 

  126. S. Konishi, S. Gotoh, K. Tateishi, Y. Yamamoto, Y. Korogi, T. Nagasaki, H. Matsumoto, S. Muro, T. Hirai, I. Ito, S. Tsukita, and M. Mishima: Directed induction of functional multi-ciliated cells in proximal airway epithelial spheroids from human pluripotent stem cells. Stem Cell Rep. 6, 18–25 (2016).

    Article  CAS  Google Scholar 

  127. S. Gotoh, I. Ito, T. Nagasaki, Y. Yamamoto, S. Konishi, Y. Korogi, H. Matsumoto, S. Muro, T. Hirai, M. Funato, S.-I. Mae, T. Toyoda, A. Sato-Otsubo, S. Ogawa, K. Osafune, and M. Mishima: Generation of alveolar epithelial spheroids via isolated progenitor cells from human pluripotent stem cells. Stem Cell Rep. 3, 394–403 (2014).

    Article  CAS  Google Scholar 

  128. B.R. Dye, D.R. Hill, M.A. Ferguson, Y.-H. Tsai, M.S. Nagy, R. Dyal, J.M. Wells, C.N. Mayhew, R. Nattiv, O.D. Klein, E.S. White, G.H. Deutsch, and J.R. Spence: In vitro generation of human pluripotent stem cell derived lung organoids. Elife 4, e05098 (2015).

    Article  Google Scholar 

  129. B.R. Dye, P.H. Dedhia, A.J. Miller, M.S. Nagy, E.S. White, L.D. Shea, and J.R. Spence: A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. Elife 5, 3025 (2016).

    Article  Google Scholar 

  130. C.E. Barkauskas, M.J. Cronce, C.R. Rackley, E.J. Bowie, D.R. Keene, B.R. Stripp, S.H. Randell, P.W. Noble, and B.L.M. Hogan: Type 2 alveolar cells are stem cells in adult lung. J. Clin. Invest. 123, 3025–3036 (2013).

    Article  CAS  Google Scholar 

  131. J.-H. Lee, D.H. Bhang, A. Beede, T.L. Huang, B.R. Stripp, K.D. Bloch, A.J. Wagers, Y.-H. Tseng, S. Ryeom, and C.F. Kim: Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell 156, 440–455 (2014).

    Article  CAS  Google Scholar 

  132. A.J. Booth, R. Hadley, A.M. Cornett, A.A. Dreffs, S.A. Matthes, J.L. Tsui, K. Weiss, J.C. Horowitz, V.F. Fiore, T.H. Barker, B.B. Moore, F.J. Martinez, L.E. Niklason, and E.S. White: Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am. J. Respir. Crit. Care Med. 186, 866–876 (2012).

    Article  CAS  Google Scholar 

  133. J.M.H. Liu, J. Zhang, X. Zhang, K.A. Hlavaty, C.F. Ricci, J.N. Leonard, L.D. Shea, and R.M. Gower: Transforming growth factor-beta 1 delivery from microporous scaffolds decreases inflammation post-implant and enhances function of transplanted islets. Biomaterials 80, 11–19 (2016).

    Article  Google Scholar 

  134. D.J. Margul, J. Park, R.M. Boehler, D.R. Smith, M.A. Johnson, D.A. McCreedy, T. He, A. Ataliwala, T.V. Kukushliev, J. Liang, A. Sohrabi, A.G. Goodman, C.M. Walthers, L.D. Shea, and S.K. Seidlits: Reducing neuroinflammation by delivery of IL-10 encoding lentivirus from multiple-channel bridges. Bioeng. Transl. Med. 1, 136–148 (2016).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biomedical Engineering, University of Michigan Biomedical Engineering, Ann Arbor, Michigan, 48109, USA

    Briana R. Dye, Tadas Kasputis & Lonnie D. Shea

  2. Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Jason R. Spence

  3. Department of Cell and Developmental Biology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Jason R. Spence

  4. Center of Organogenesis, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Jason R. Spence

Authors
  1. Briana R. Dye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tadas Kasputis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jason R. Spence
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lonnie D. Shea
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lonnie D. Shea.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dye, B.R., Kasputis, T., Spence, J.R. et al. Take a deep breath and digest the material: organoids and biomaterials of the respiratory and digestive systems. MRS Communications 7, 502–514 (2017). https://doi.org/10.1557/mrc.2017.61

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1557/mrc.2017.61

Search

Navigation