Skip to main content
SpringerLink
Log in

Encapsulation of Stem Cells in Research and Therapy

  • Chapter
  • First Online:
Biological, Physical and Technical Basics of Cell Engineering

Abstract

As stem cell therapies advance, rethinking of medical device engineering provides promise for treatment options in clinical applications. In the past decades, cell transplantation has been an approach for many regenerative therapies. To date, however, limited human donor supply has hampered the transplantation of human organs and mature donor tissues for an increasing number of patients worldwide, particularly those with liver and pancreatic diseases. This chapter explores the use of stem cells as an alternative to implantation of mature cells and discusses the development of stem cell therapies that may promote organ regeneration, or delivery of endocrine products in vivo, and their challenges for the use in clinical applications. Aspects of stem cell differentiation strategies, microenvironmental factors, and cellular immunity are addressed. A second limitation to cellular transplantation has been the need for chronic immunosuppression. As an alternative to clinical immunosuppression, designs and materials for cellular encapsulation, intended to avoid rejection by the immune system and to control growth of cellular implants, have been developed. Liver disease is chosen to show examples of stem cell micro-encapsulation approaches in research and therapy. Secondly, a stem cell macro-encapsulation device is used as an example for a bio-artificial pancreas as a possible therapeutic approach for diabetes mellitus. The focus of this chapter is on the synergy between stem cell therapy and medical device engineering as a multi-disciplinary approach in the field of bioengineering, which may eventually provide new options for treatment of human disease.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ECM:

Extra Cellular Matrix

hESC:

Human Embryonic Stem Cell

iPSC:

Induced Pluripotent Stem Cell

LPC:

Liver Progenitor Cell

MSC:

Mesenchymal Stem Cell

PPC:

Pancreatic Progenitor Cell

References

  1. Everhart, J. E., & Ruhl, C. E. (2009). Burden of digestive diseases in the United States part III: Liver, biliary tract, and pancreas. Gastroenterology, 136(4), 1134–1144.

    Article  Google Scholar 

  2. Yadav, D., & Lowenfels, A. B. (2013). The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology, 144(6), 1252–1261.

    Article  Google Scholar 

  3. Congress, I. L. (2016). Fast facts about liver disease—The international Liver Congress 2016, April 13–17. The Home of Hepatology. http://2016.ilc-congress.eu/wp-content/uploads/2016/04/Liver-disease-backgrounder.pdf.

  4. Blachier, M., Leleu, H., Peck-Radosavljevic, M., Valla, D. C., & Roudot-Thoraval, F. (2013). The burden of liver disease in Europe: A review of available epidemiological data. Journal of hepatology, 58(3), 593–608.

    Article  Google Scholar 

  5. Lévy, P., Domínguez-Muñoz, E., Imrie, C., Löhr, M., & Maisonneuve, P. (2014) Epidemiology of chronic pancreatitis: burden of the disease and consequences. United European Gastroenterology Journal, 2(5), 345–354.

    Article  Google Scholar 

  6. Peery, A. F., Crockett, S. D., Barritt, A. S., Dellon, E. S., Eluri, S., Gangarosa, L. M., … Schmidt, M. (2015). Burden of Gastrointestinal, Liver, and Pancreatic Diseases in the United States. Gastroenterology, 149(7), 1731–1741 e3.

    Google Scholar 

  7. Zaret, K. S. (2008). Genetic programming of liver and pancreas progenitors: Lessons for stem-cell differentiation. Nature Reviews Genetics, 9(5), 329–340.

    Article  Google Scholar 

  8. Rous, P., & Murphy, J. B. (1912). The histological signs of resistance to a transmissible sarcoma of the fowl. Journal of Experimental Medicine, 15(3), 270–286.

    Article  Google Scholar 

  9. Bisceglie, V. (1933). Uber die antineoplastische Immunitat: (I) Heterologe Einpflanzung von Tumoren in Huhnerembryonen. Zeitschrift für Krebsforschung, 40, 122–140.

    Article  Google Scholar 

  10. Bisceglie, V. (1933). Uber die antineoplastische Immunität; (II) Die Wachstumfahigkeit von heterologen Geschwulsten in erwachsenen Tieren nach Einpflanzung in Kollodiumsackchen. Zeitschrift für Krebsforschung, 40, 141–158.

    Article  Google Scholar 

  11. Chang, T. M. (1964). Semipermeable microcapsules. Science, 146(3643), 524–525.

    Article  Google Scholar 

  12. Federlin, K., & Raptis, S. (2001). Ernst F. Pfeiffer: His impact on diabetes research and treatment over the last 45 years. Experimental and Clinical Endocrinology & Diabetes, 109(2), S83–S85.

    Article  Google Scholar 

  13. Bowen, K. M., Andrus, L., & Lafferty, K. J. (1980). Successful allotransplantation of mouse pancreatic islets to nonimmunosuppressed recipients. Diabetes, 29(1), 98–104.

    Article  Google Scholar 

  14. Lafferty, K. J., Andrus, L., & Prowse, S. J. (1980). Role of lymphokine and antigen in the control of specific T cell responses. Immunological Reviews, 51, 279–314.

    Article  Google Scholar 

  15. Chick, W. L., Perna, J. J., Lauris, V., Low, D., Galletti, P. M., Panol, G., et al. (1977). Artificial pancreas using living beta cells: Effects on glucose homeostasis in diabetic rats. Science, 197(4305), 4780–4782.

    Article  Google Scholar 

  16. Lim, F., & Sun, A. M. (1980). Microencapsulated islets as bioartificial endocrine pancreas. Science, 210(4472), 908–910.

    Article  Google Scholar 

  17. Cima, L. G., Vacanti, J. P., Vacanti, C., Ingber, D., Mooney, D., & Langer, R. (1991). Tissue engineering by cell transplantation using degradable polymer substrates. Journal of Biomechanical Engineering, 113(2), 143–151.

    Article  Google Scholar 

  18. https://ki.mit.edu/people/faculty/langer. Robert S. Langer. 2017.

  19. Krishnan, R., Alexander, M., Robles, L., Foster III, C. E., & Lakey, J. R. (2014). Islet and stem cell encapsulation for clinical transplantation. The Review of Diabetic Studies, 11(1), 84–101.

    Article  Google Scholar 

  20. Soon-Shiong, P., Heintz, R. E., Merideth, N., Yao, Q. X., Yao, Z., Zheng, T. I. A. N. L. I., … Mendez, R. (1994). Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet, 343(8903), 950–951.

    Google Scholar 

  21. Calafiore, R., Basta, G., Luca, G., Lemmi, A., Montanucci, M. P., Calabrese, G., … Brunetti, P. (2006). Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: first two cases. Diabetes Care, 29(1), 137–138.

    Article  Google Scholar 

  22. Löhr, M., Bago, Z. T., Bergmeister, H., Ceijna, M., Freund, M., Gelbmann, W., … Henninger, W. (1999). Cell therapy using microencapsulated 293 cells transfected with a gene construct expressing CYP2B1, an ifosfamide converting enzyme, instilled intra-arterially in patients with advanced-stage pancreatic carcinoma: a phase I/II study. Journal of Molecular Medicine, 77(4), 393–398.

    Google Scholar 

  23. Löhr, M., Hoffmeyer, A., Kröger, J. C., Freund, M., Hain, J., Holle, A., … Nizze, H. (2001). Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma. Lancet, 357(9268), 1591–1592.

    Article  Google Scholar 

  24. Löhr, M., Kroger, J. C., Hoffmeyer, A., Freund, M., Hain, J., Holle, A., … Saller, R. (2003). Safety, feasibility and clinical benefit of localized chemotherapy using microencapsulated cells for inoperable pancreatic carcinoma in a phase I/II trial. Cancer Therapy, 1, 121–131.

    Google Scholar 

  25. Pelegrin, M., Marin, M., Noel, D., Del Rio, M., Saller, R., Stange, J., … Piechaczyk, M. (1998). Systemic long-term delivery of antibodies in immunocompetent animals using cellulose sulphate capsules containing antibody-producing cells. Gene Therapy, 5(6), 828–834.

    Article  Google Scholar 

  26. Hartgerink, J. D., Beniash, E., & Stupp, S. I. (2001). Self-assembly and mineralization of peptide-amphiphile nanofibers. Science, 294(5547), 1684–1688.

    Article  Google Scholar 

  27. Kobayashi, T., Aomatsu, Y., Iwata, H., Kin, T., Kanehiro, H., Hisanaga, M., … Nakajima, Y. (2003). Indefinite islet protection from autoimmune destruction in nonobese diabetic mice by agarose microencapsulation without immunosuppression. Transplantation, 75(5), 619–625.

    Article  Google Scholar 

  28. Haque, T., Chen, H., Ouyang, W., Martoni, C., Lawuyi, B., Urbanska, A. M., & Prakash, S. (2005). In vitro study of alginate-chitosan microcapsules: an alternative to liver cell transplants for the treatment of liver failure. Biotechnology Letters, 27(5), 317–322.

    Article  Google Scholar 

  29. Young, S., Wong, M., Tabata, Y., & Mikos, A. G. (2005). Gelatin as a delivery vehicle for the controlled release of bioactive molecules. Journal of Controlled Release, 109(1–3), 256–274.

    Article  Google Scholar 

  30. Dong, H., Fahmy, T. M., Metcalfe, S. M., Morton, S. L., Dong, X., Inverardi, L., … Wang, H. (2012). Immuno-isolation of pancreatic islet allografts using pegylated nanotherapy leads to long-term normoglycemia in full MHC mismatch recipient mice. PLoS One, 7(12), e50265.

    Article  Google Scholar 

  31. Kim, A. R., Hwang, J. H., Kim, H. M., Kim, H. N., Song, J. E., Yang, Y. I., … Khang, G. (2013). Reduction of inflammatory reaction in the use of purified alginate microcapsules. Journal of Biomaterials Science, Polymer Edition, 24(9), 1084–1098.

    Article  Google Scholar 

  32. Hueck, I. S., Haas, M., Finones, R., Frimodig, J., & Gough, D. A. (2011). The potential of selectively cultured adult stem cells re-implanted in tissues. In Artmann (Ed.), Stem cell engineering: Principles and applications (pp. 79–117). Berlin: Springer.

    Google Scholar 

  33. Seale, N. M., & Varghese, S. (2016). Biomaterials for pluripotent stem cell engineering: from fate determination to vascularization. Journal of Materials Chemistry B, 4(20), 3454–3463.

    Article  Google Scholar 

  34. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861–872.

    Article  Google Scholar 

  35. Aasen, T., Raya, A., Barrero, M. J., Garreta, E., Consiglio, A., Gonzalez, F., … Edel, M. (2008). Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology, 26(11), 1276–1284.

    Article  Google Scholar 

  36. Loh, Y. H., Hartung, O., Li, H., Guo, C., Sahalie, J. M., Manos, P. D., … Lensch, M. W. (2010). Reprogramming of T cells from human peripheral blood. Cell Stem Cell, 7(1), 15–19.

    Article  Google Scholar 

  37. Zhou, T., Benda, C., Dunzinger, S., Huang, Y., Ho, J. C., Yang, J., … Bao, X. (2012). Generation of human induced pluripotent stem cells from urine samples. Nature Protocols, 7(12), 2080–2089.

    Article  Google Scholar 

  38. Selvaraj, V., Plane, J. M., Williams, A. J., & Deng, W. (2010). Switching cell fate: the remarkable rise of induced pluripotent stem cells and lineage reprogramming technologies. Trends in Biotechnology, 28(4), 214–223.

    Article  Google Scholar 

  39. Liu, H., Ye, Z., Kim, Y., Sharkis, S., & Jang, Y. Y. (2010). Generation of endoderm-derived human induced pluripotent stem cells from primary hepatocytes. Hepatology, 51(5), 1810–1819.

    Article  Google Scholar 

  40. Sullivan, G. J., Hay, D. C., Park, I. H., Fletcher, J., Hannoun, Z., Payne, C. M., … Wang, G. (2010). Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology, 51(1), 329–335.

    Article  Google Scholar 

  41. Wu, S., Xu, H., Chen, B., Wen, Y., Ikusika, O. M., Ocker, A., … Ildstad, S. T. (2011). Sensitized recipients exhibit accelerated but not hyperacute rejection of vascularized composite tissue allografts. Transplantation, 92(6), 627–633.

    Article  Google Scholar 

  42. Yamanaka, S. (2012). Induced pluripotent stem cells: Past, present, and future. Cell Stem Cell, 10(6), 678–684.

    Article  Google Scholar 

  43. Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., … Marshak, D. R. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284(5411), 143–147.

    Article  Google Scholar 

  44. Kadam, S., Muthyala, S., Nair, P., & Bhonde, R. (2010). Human placenta-derived mesenchymal stem cells and islet-like cell clusters generated from these cells as a novel source for stem cell therapy in diabetes. The Review of Diabetic Studies, 7(2), 168–182.

    Article  Google Scholar 

  45. Ngoc, P. K., Van Phuc, P., Nhung, T. H., Thuy, D. T., & Nguyet, N. T. M. (2011). Improving the efficacy of type 1 diabetes therapy by transplantation of immunoisolated insulin-producing cells. Human Cell, 24(2), 86–95.

    Article  Google Scholar 

  46. Goren, A., Dahan, N., Goren, E., Baruch, L., & Machluf, M. (2010). Encapsulated human mesenchymal stem cells: a unique hypoimmunogenic platform for long-term cellular therapy. FASEB J, 24(1), 22–31.

    Article  Google Scholar 

  47. Wilson, J. L., & McDevitt, T. C. (2013). Stem cell microencapsulation for phenotypic control, bioprocessing, and transplantation. Biotechnology and Bioengineering, 110(3), 667–682.

    Article  Google Scholar 

  48. Baraniak, P. R., & McDevitt, T. C. (2010). Stem cell paracrine actions and tissue regeneration. Regenerative Medicine, 5(1), 121–143.

    Article  Google Scholar 

  49. Orive, G., Gascón, A. R., Hernández, R. M., Igartua, M., & Pedraz, J. L. (2003). Cell microencapsulation technology for biomedical purposes: Novel insights and challenges. Trends in Pharmacological Sciences, 24(5), 207–210.

    Article  Google Scholar 

  50. Hunkeler, D. (2001). Allo transplants xeno: As bioartificial organs move to the clinic. Introduction. Annals of the New York Academy of Sciences, 944, 1–6.

    Article  Google Scholar 

  51. Kang, H. K., Wang, S., Dangi, A., Zhang, X., Singh, A., Zhang, L., … Thorp, E. B. (2017). Differential role of B cells and IL-17 versus IFN-gamma during early and late rejection of pig islet xenografts in mice. Transplantation.

    Google Scholar 

  52. Dufrane, D., & Gianello, P. (2012). Pig islet for xenotransplantation in human: Structural and physiological compatibility for human clinical application. Transplantation Reviews, 26(3), 183–188.

    Article  Google Scholar 

  53. Dufrane, D., & Gianello, P. (2012). Macro- or microencapsulation of pig islets to cure type 1 diabetes. World Journal of Gastroenterology, 18(47), 6885–6893.

    Article  Google Scholar 

  54. Zhu, H. T., Lu, L., Liu, X. Y., Yu, L., Lyu, Y., & Wang, B. (2015). Treatment of diabetes with encapsulated pig islets: An update on current developments. Journal of Zhejiang University-Science B, 16(5), 329–343.

    Article  Google Scholar 

  55. Gunzburg, W. H., & Salmons, B. (2000). Xenotransplantation: Is the risk of viral infection as great as we thought? Molecular Medicine Today, 6(5), 199–208.

    Article  Google Scholar 

  56. Bowie, K. M., & Chang, P. L. (1998). Development of engineered cells for implantation in gene therapy. Advanced Drug Delivery Reviews, 33(1–2), 31–43.

    Google Scholar 

  57. Uludag, H., De Vos, P., & Tresco, P. A. (2000). Technology of mammalian cell encapsulation. Advanced Drug Delivery Reviews, 42(1–2), 29–64.

    Article  Google Scholar 

  58. Sakai, S., Mu, C., Kawabata, K., Hashimoto, I., & Kawakami, K. (2006). Biocompatibility of subsieve-size capsules versus conventional-size microcapsules. Journal of Biomedical Materials Research Part A, 78(2), 394–398.

    Article  Google Scholar 

  59. Fang, S., & MAO, L. (2007). Differentiation of embryoid-body cells derived from embryonic stem cells into hepatocytes in alginate microbeads in vitro. Acta Pharmacologica Sinica, 28(12), 1924–1930.

    Article  Google Scholar 

  60. Orive, G., Hernández, R. M., Gascón, A. R., Calafiore, R., Chang, T. M. S., de Vos, P., … Pedraz, J. L. (2004). History, challenges and perspectives of cell microencapsulation. Trends in Biotechnology, 22(2), 87–92.

    Article  Google Scholar 

  61. Rabanel, J. M., Banquy, X., Zouaoui, H., Mokhtar, M., & Hildgen, P. (2009). Progress technology in microencapsulation methods for cell therapy. Biotechnology Progress, 25(4), 946–963.

    Article  Google Scholar 

  62. Kidd, K. R., Nagle, R. B., & Williams, S. K. (2002). Angiogenesis and neovascularization associated with extracellular matrix-modified porous implants. Journal of Biomedical Materials Research, 59(2), 366–377.

    Article  Google Scholar 

  63. Vasanthan, K. S., Subramanian, A., Krishnan, U. M., & Sethuraman, S. (2012). Role of biomaterials, therapeutic molecules and cells for hepatic tissue engineering. Biotechnology Advances, 30(3), 742–752.

    Article  Google Scholar 

  64. Maguire, T., Davidovich, A. E., Wallenstein, E. J., Novik, E., Sharma, N., Pedersen, H., … Yarmush, M. (2007). Control of hepatic differentiation via cellular aggregation in an alginate microenvironment. Biotechnology and Bioengineering, 98(3), 631–644.

    Article  Google Scholar 

  65. Shi, X. L., Zhang, Y., Gu, J. Y., & Ding, Y. T. (2009). Coencapsulation of hepatocytes with bone marrow mesenchymal stem cells improves hepatocyte-specific functions. Transplantation, 88(10), 1178–1185.

    Article  Google Scholar 

  66. Gattazzo, F., Urciuolo, A., & Bonaldo, P. (2014). Extracellular matrix: A dynamic microenvironment for stem cell niche. Biochimica et Biophysica Acta, 1840(8), 2506–2519.

    Article  Google Scholar 

  67. Vishwakarma, A., & Karp, J. M. (Eds.) (2017). Biology and engineering of stem cell niches. London: Elsevier Academic Press.

    Google Scholar 

  68. Jhala, D., & Vasita, R. (2015). A review on extracellular matrix mimicking strategies for an artificial stem cell niche. Polymer Reviews, 55(4), 561–595.

    Article  Google Scholar 

  69. Scadden, D. T. (2006). The stem-cell niche as an entity of action. Nature, 441(7097), 1075–1079.

    Article  Google Scholar 

  70. Stoker, M., & Gherardi, E. (1991). Regulation of cell movement: The motogenic cytokines. Biochimica et Biophysica Acta, 1072(1), 81–102.

    Google Scholar 

  71. Welf, E. S., & Haugh, J. M. (2011). Signaling pathways that control cell migration: Models and analysis. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 3(2), 231–240.

    Google Scholar 

  72. Watt, F. M., & Huck, W. T. (2013). Role of the extracellular matrix in regulating stem cell fate. Nature Reviews Molecular Cell Biology, 14(8), 467–473.

    Article  Google Scholar 

  73. Rowley, J. A., & Mooney, D. J. (2002). Alginate type and RGD density control myoblast phenotype. Journal of Biomedical Materials Research, 60(2), 217–223.

    Article  Google Scholar 

  74. Benoit, D. S., Schwartz, M. P., Durney, A. R., & Anseth, K. S. (2008). Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nature Materials, 7(10), 816–823.

    Article  Google Scholar 

  75. Chokkalingam, V., Tel, J., Wimmers, F., Liu, X., Semenov, S., Thiele, J., … Huck, W. T. (2013). Probing cellular heterogeneity in cytokine-secreting immune cells using droplet-based microfluidics. Lab on a Chip, 13(24), 4740–4744.

    Article  Google Scholar 

  76. Severian Dumitriu, V. P. (2013) Medical and pharmaceutical applications, Vol. 2, 3rd ed. ISBN 978-1-4200-9468-8.

    Google Scholar 

  77. Brandtner, D. (2013). Bioencapsulation of living cells for diverse medical applications. Bentham books. ISBN: 978-1-60805-721-4.

    Google Scholar 

  78. Strand, B. L., Ryan, L., Veld, P. I. T., Kulseng, B., Rokstad, A. M., Skjåk-Bræk, G., & Espevik, T. (2001). Poly-L-Lysine induces fibrosis on alginate microcapsules via the induction of cytokines. Cell Transplant, 10(3), 263–275.

    Article  Google Scholar 

  79. Liu, Z. C., & Chang, T. M. (2002). Increased viability of transplanted hepatocytes when hepatocytes are co-encapsulated with bone marrow stem cells using a novel method. Artificial Cells, Blood Substitutes, and Immobilization Biotechnology, 30(2), 99–112.

    Article  Google Scholar 

  80. Otterlei, M., Østgaard, K., Skjåk-Bræk, G., Smidsrød, O., Soon-Shiong, P., & Espevik, T. (1991). Induction of cytokine production from human monocytes stimulated with alginate. Journal of Immunotherapy, 10(4), 286–291.

    Article  Google Scholar 

  81. Espevik, T., Otterlei, M., Skjåk‐Braek, G., Ryan, L., Wright, S. D., & Sundan, A. (1993). The involvement of CD14 in stimulation of cytokine production by uronic acid polymers. European Journal of Immunology, 23(1), 255–261.

    Article  Google Scholar 

  82. Aiedehe, K., Gianasii, E., Orienti, I., & Zecchi, V. (1997). Chitosan microcapsules as controlled release systems for insulin. Journal of Microencapsulation, 14(5), 567–576.

    Article  Google Scholar 

  83. Altiok, D., Altiok, E., & Tihminlioglu, F. (2010). Physical, antibacterial and antioxidant properties of chitosan films incorporated with thyme oil for potential wound healing applications. Journal of Materials Science. Materials in Medicine, 21(7), 2227–2236.

    Article  Google Scholar 

  84. Green, D. W., Leveque, I., Walsh, D., Howard, D., Yang, X., Partridge, K., … Oreffo, R. O. (2005). Polysaccharide capsules for encapsulation, organization, and delivery of human cell types and growth factors. Advanced Funtional Materials, 15(6), 917–923.

    Article  Google Scholar 

  85. Krasaekoopt, W., Bhandari, B., & Deeth, H. (2004). The influence of coating materials on some properties of alginate beads and survivability of microencapsulated probiotic bacteria. International Dairy Journal, 14(8), 737–743.

    Article  Google Scholar 

  86. Chen, H., Ouyang, W., Jones, M., Metz, T., Martoni, C., Haque, T., … Prakash, S. (2007). Preparation and characterization of novel polymeric microcapsules for live cell encapsulation and therapy. Cell Biochemistry and Biophysics, 47(1), 159–168.

    Article  Google Scholar 

  87. Tan, W., Krishnaraj, R., & Desai, T. A. (2001). Evaluation of nanostructured composite collagen–chitosan matrices for tissue engineering. Tissue Engineering, 7(2), 203–210.

    Article  Google Scholar 

  88. Chevallay, B., & Herbage, D. (2000). Collagen-based biomaterials as 3D scaffold for cell cultures: Applications for tissue engineering and gene therapy. Medical and Biological Engineering and Computing, 38(2), 211–218.

    Article  Google Scholar 

  89. Malafaya, P. B., Silva, G. A., & Reis, R. L. (2007). Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Advanced Drug Delivery Reviews, 59(4–5), 207–233.

    Article  Google Scholar 

  90. Dautzenberg, H., Schuldt, U. T. E., Grasnick, G., Karle, P., MÜller, P., LÖhr, M., … Salmons, B. (1999). Development of cellulose sulfate-based polyelectrolyte complex microcapsules for medical applications. Annals of the New York Academy of Sciences, 875, 46–63.

    Article  Google Scholar 

  91. Swioklo, S., & Connon, C. J. (2016). Keeping cells in their place: The future of stem cell encapsulation. Expert Opinion on Biological Therapy, 16(10), 1181–1183.

    Article  Google Scholar 

  92. Higgins, C. C. (1931). Solitary cysts of the kidney. Annals of Surgery, 93(4), 868–879.

    Article  Google Scholar 

  93. Byass, P. (2014). The global burden of liver disease: A challenge for methods and for public health. BMC Medicine, 12, 159.

    Article  Google Scholar 

  94. Hindley, C. J., Cordero-Espinoza, L., & Huch, M. (2016). Organoids from adult liver and pancreas: Stem cell biology and biomedical utility. Development Biology, 420(2), 251–261.

    Article  Google Scholar 

  95. Fox, I. J., & Chowdhury, J. R. (2004). Hepatocyte transplantation. American Journal of Transplantation, 4(6), 7–13.

    Article  Google Scholar 

  96. Sell, S. (2001). Heterogeneity and plasticity of hepatocyte lineage cells. Hepatology, 33(3), 738–750.

    Article  Google Scholar 

  97. Miyajima, A., Tanaka, M., & Itoh, T. (2014). Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. Cell Stem Cell, 14(5), 561–574.

    Article  Google Scholar 

  98. Itoh (2015). Tissue-specific stem cell niche, stem cell biology and regeneration ed. K. Turksen. Switzerland: Springer.

    Google Scholar 

  99. Conigliaro, A., Brenner, D. A., & Kisseleva, T. (2010). Hepatic progenitors for liver disease: Current position. Stem Cells Cloning, 3, 39–47.

    Google Scholar 

  100. Yang, W., Yan, H. X., Chen, L., Liu, Q., He, Y. Q., Yu, L. X., .… Chen, C. (2008). Wnt/beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells. Cancer Research, 68(11), 4287–4295.

    Article  Google Scholar 

  101. de Lau, W., Barker, N., Low, T. Y., Koo, B. K., Li, V. S., Teunissen, H., … Stange, D. E. (2011). Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature, 476(7360). 293–297.

    Article  Google Scholar 

  102. Boulter, L., Govaere, O., Bird, T. G., Radulescu, S., Ramachandran, P., Pellicoro, A., … Sansom, O. J. (2012). Macrophage-derived Wnt opposes notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nature Medicine, 18(4), 572–579.

    Article  Google Scholar 

  103. Huch, M., Dorrell, C., Boj, S. F., Van Es, J. H., Li, V. S., Van De Wetering, M., … Haft, A. (2013). In vitro expansion of single Lgr5 + liver stem cells induced by Wnt-driven regeneration. Nature, 494(7436), 247–250.

    Article  Google Scholar 

  104. Xinguang, Y., Huixing, Y., Xiaowei, W., Xiaojun, W., & Linghua, Y. (2015). R-spondin1 arguments hepatic fibrogenesis in vivo and in vitro. Journal of Surgical Research, 193(2), 598–605.

    Article  Google Scholar 

  105. Kopp, J. L., Grompe, M., & Sander, M. (2016). Stem cells versus plasticity in liver and pancreas regeneration. Nature Cell Biology, 18(3), 238–245.

    Article  Google Scholar 

  106. Yanger, K., Knigin, D., Zong, Y., Maggs, L., Gu, G., Akiyama, H., … Stanger, B. Z. (2014). Adult hepatocytes are generated by self-duplication rather than stem cell differentiation. Cell Stem Cell, 15(3), 340–349.

    Article  Google Scholar 

  107. Tarlow, B. D., Pelz, C., Naugler, W. E., Wakefield, L., Wilson, E. M., Finegold, M. J., & Grompe, M. (2014). Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes. Cell Stem Cell, 15(5), 605–618.

    Article  Google Scholar 

  108. Ji, J., & Wang, X. W. (2012). Clinical implications of cancer stem cell biology in hepatocellular carcinoma. Seminars in Oncology, 39(4), 461–472.

    Article  Google Scholar 

  109. Di Bonzo, L. V., Ferrero, I., Cravanzola, C., Mareschi, K., Rustichell, D., Novo, E., … Davit, A. (2008). Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: Engraftment and hepatocyte differentiation versus profibrogenic potential. Gut, 57(2), 223–231.

    Google Scholar 

  110. Cai, J., Zhao, Y., Liu, Y., Ye, F., Song, Z., Qin, H., … Guo, Y. (2007). Directed differentiation of human embryonic stem cells into functional hepatic cells. Hepatology, 45(5), 1229–1239.

    Article  Google Scholar 

  111. Basma, H., Soto–Gutiérrez, A., Yannam, G. R., Liu, L., Ito, R., Yamamoto, T., … Muirhead, D. (2009). Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology, 136(3), 990–999.

    Article  Google Scholar 

  112. Touboul, T., Hannan, N. R., Corbineau, S., Martinez, A., Martinet, C., Branchereau, S., … Weber, A. (2010). Generation of functional hepatocytes from human embryonic stem cells under chemically defined conditions that recapitulate liver development. Hepatology, 51(5), 1754–1765.

    Article  Google Scholar 

  113. Magyar, J. P., Nemir, M., Ehler, E., Suter, N., Perriard, J. C., & Eppenberger, H. M. (2001). Mass production of embryoid bodies in microbeads. Annals of the New York Academy of Sciences, 944(1), 135–143.

    Article  Google Scholar 

  114. Cho, N. J., Elazar, M., Xiong, A., Lee, W., Chiao, E., Baker, J., … Glenn, J. S. (2008). Viral infection of human progenitor and liver-derived cells encapsulated in three-dimensional PEG-based hydrogel. Biomedical materials, 4(1), 011001.

    Article  Google Scholar 

  115. Meier, R. P., Mahou, R., Morel, P., Meyer, J., Montanari, E., Muller, Y. D., … Bühler, L. H. (2015). Microencapsulated human mesenchymal stem cells decrease liver fibrosis in mice. Journal of Hepatology, 62(3), 634–641.

    Article  Google Scholar 

  116. Meier, R. P., Montanari, E., Morel, P., Pimenta, J., Schuurman, H. J., Wandrey, C., … Bühler, L. H. (2017). Microencapsulation of hepatocytes and mesenchymal stem cells for therapeutic applications. Hepatocyte Transplantation: Methods and Protocols, 259–271.

    Google Scholar 

  117. Kisseleva, T., Uchinami, H., Feirt, N., Quintana-Bustamante, O., Segovia, J. C., Schwabe, R. F., & Brenner, D. A. (2006). Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis. Journal of hepatology, 45(3), 429–438.

    Article  Google Scholar 

  118. Maguire, T., Novik, E., Schloss, R., & Yarmush, M. (2006). Alginate-PLL microencapsulation: Effect on the differentiation of embryonic stem cells into hepatocytes. Biotechnology and Bioengineering, 93(3). 581–591.

    Article  Google Scholar 

  119. Fang, S., & MAO, L. (2007). Differentiation of embryoid-body cells derived from embryonic stem cells into hepatocytes in alginate microbeads in vitro. Acta Pharmacologica Sinica, 28(12), 1924–1930.

    Article  Google Scholar 

  120. Palakkan, A. A., Hay, D. C., TV, K., & Ross, J. A. (2013). Liver tissue engineering and cell sources: Issues and challenges. Liver International, 33(5), 666–676.

    Article  Google Scholar 

  121. Kirk, K., Hao, E., Lahmy, R., & Itkin-Ansari, P. (2014). Human embryonic stem cell derived islet progenitors mature inside an encapsulation device without evidence of increased biomass or cell escape. Stem Cell Research, 12(3), 807–814.

    Article  Google Scholar 

  122. Scharp, D. W., & Marchetti, P. (2014). Encapsulated islets for diabetes therapy: History, current progress, and critical issues requiring solution. Advanced Drug Delivery Reviews, 67–68, 35–73.

    Article  Google Scholar 

  123. Sakata, N., Sumi, S., Yoshimatsu, G., Goto, M., Egawa, S., & Unno, M. (2012). Encapsulated islets transplantation: Past, present and future. World Journal of Gastrointestinal Pathophysiology, 3(1), 19–26.

    Article  Google Scholar 

  124. Kirchhof, N., Shibata, S., Wijkstrom, M., Kulick, D. M., Salerno, C. T., Clemmings, S. M., … Hering, B. J. (2004). Reversal of diabetes in non-immunosuppressed rhesus macaques by intraportal porcine islet xenografts precedes acute cellular rejection. Xenotransplantation, 11(5), 396–407.

    Article  Google Scholar 

  125. Elliott, R. B., Escobar, L., Tan, P. L. J., Garkavenko, O., Calafiore, R., Basta, P., … Bambra, C. (2005, October). Intraperitoneal alginate-encapsulated neonatal porcine islets in a placebo-controlled study with 16 diabetic cynomolgus primates. Transplantation Proceedings, 37(8), 3505–3508.

    Article  Google Scholar 

  126. Duvivier‐Kali, V. F., Omer, A., Lopez‐Avalos, M. D., O’neil, J. J., & Weir, G. C. (2004). Survival of microencapsulated adult pig islets in mice in spite of an antibody response. American Journal of Transplantation, 4(12), 1991–2000.

    Article  Google Scholar 

  127. Elliott, R. B., Escobar, L., Tan, P. L., Muzina, M., Zwain, S., & Buchanan, C. (2007). Live encapsulated porcine islets from a type 1 diabetic patient 9.5 yr after xenotransplantation. Xenotransplantation, 14(2), 157–161.

    Article  Google Scholar 

  128. Tuch, B. E., Keogh, G. W., Williams, L. J., Wu, W., Foster, J. L., Vaithilingam, V., & Philips, R. (2009). Safety and viability of microencapsulated human islets transplanted into diabetic humans. Diabetes Care, 32(10), 1887–1889.

    Article  Google Scholar 

  129. King, A., Lau, J., Nordin, A., Sandler, S., & Andersson, A. (2003). The effect of capsule composition in the reversal of hyperglycemia in diabetic mice transplanted with microencapsulated allogeneic islets. Diabetes Technology & Therapeutics, 5(4), 653–663.

    Article  Google Scholar 

  130. King, A., Andersson, A., Strand, B. L., Lau, J., Skjåk-Bræk, G., & Sandler, S. (2003). The role of capsule composition and biologic responses in the function of transplanted microencapsulated islets of Langerhans. Transplantation, 76(2), 275–279.

    Article  Google Scholar 

  131. Kulseng, B., Thu, B., Espevik, T., & Skjåk-Bræk, G. (1997). Alginate polylysine microcapsules as immune barrier: Permeability of cytokines and immunoglobulins over the capsule membrane. Cell Transplant, 6(4), 387–394.

    Article  Google Scholar 

  132. Juste, S., Lessard, M., Henley, N., Ménard, M., & Hallé, J. P. (2005). Effect of poly-L-lysine coating on macrophage activation by alginate-based microcapsules: Assessment using a new in vitro method. Journal of Biomedical Materials Research Part A, 72(4), 389–398.

    Article  Google Scholar 

  133. Pueyo, M. E., Darquy, S., Capron, F., & Reach, G. (1994). In vitro activation of human macrophages by alginate-polylysine microcapsules. Journal of Biomaterials Science, Polymer Edition, 5(3), 197–203.

    Article  Google Scholar 

  134. Brennan, D. C., Shannon, M. B., Koch, M. J., Polonsky, K. S., Desai, N., & Shapiro, J. (2004). Portal vein thrombosis complicating islet transplantation in a recipient with the Factor V Leiden mutation. Transplantation, 78(1), 172–173.

    Article  Google Scholar 

  135. Kawahara, T., Kin, T., Kashkoush, S., Gala‐Lopez, B., Bigam, D. L., Kneteman, N. M., … Shapiro, A. J. (2011). Portal vein thrombosis is a potentially preventable complication in clinical islet transplantation. American Journal of Transplantation, 11(12), 2700-2707.

    Article  Google Scholar 

  136. Sakata, N., Tan, A., Chan, N., Obenaus, A., Mace, J., Peverini, R., … Hathout, E. (2009, February). Efficacy comparison between intraportal and subcapsular islet transplants in a murine diabetic model. Transplantation Proceedings, 41(1), 346–349.

    Article  Google Scholar 

  137. Christoffersson, G., Carlsson, P. O., & Phillipson, M. (2011). Intramuscular islet transplantation promotes restored islet vascularity. Islets, 3(2), 69–71.

    Article  Google Scholar 

  138. McQuilling, J. P., Arenas-Herrera, J., Childers, C., Pareta, R. A., Khanna, O., Jiang, B., … Opara, E. C. (2011, November). New alginate microcapsule system for angiogenic protein delivery and immunoisolation of islets for transplantation in the rat omentum pouch. Transplantation Proceedings, 43(9), 3262–3264.

    Article  Google Scholar 

  139. Elliott, R. B., Escobar, L., Calafiore, R., Basta, G., Garkavenko, O., Vasconcellos, A., et al. (2005). Transplantation of micro- and macroencapsulated piglet islets into mice and monkeys. Transplantation Proceedings, 37(1), 466–469.

    Article  Google Scholar 

  140. Dufrane, D., van Steenberghe, M., Goebbels, R. M., Saliez, A., Guiot, Y., & Gianello, P. (2006). The influence of implantation site on the biocompatibility and survival of alginate encapsulated pig islets in rats. Biomaterials, 27(17), 3201–3208.

    Article  Google Scholar 

  141. Algire, G. (1943). An adaptation of the transparent-chamber technique to the mouse. Journal of the National Cancer Institute, 1943(4), 1–11.

    Google Scholar 

  142. Storrs, R., Dorian, R., King, S. R., Lakey, J., & Rilo, H. (2001). Preclinical development of the Islet sheet. Annals of the New York Academy of Sciences, 2001(944), 252–266.

    Google Scholar 

  143. Nyitray, C. E., Chavez, M. G., & Desai, T. A. (2014). Compliant 3D microenvironment improves beta-cell cluster insulin expression through mechanosensing and beta-catenin signaling. Tissue Engineering Part A, 20(13–14), 1888–1895.

    Article  Google Scholar 

  144. de Vos, P., Hamel, A. F., & Tatarkiewicz, K. (2002). Considerations for successful transplantation of encapsulated pancreatic islets. Diabetologia, 45(2), 159–173.

    Article  Google Scholar 

  145. Veriter, S., Aouassar, N., Xhema, D., Beaurin, G., Adnet, P. Y., Igarashi, Y., … Dufrane, D. (2011). Islets and mesenchymal stem cells co-encapsulation can improve subcutaneous bioartificial pancreas survival in diabetic primates. The Transplantation Society: CTS-IXA. Parallel Session 5—ISLET xenotransplantation—Preclinical models.

    Google Scholar 

  146. Davis, N. E., Beenken-Rothkopf, L. N., Mirsoian, A., Kojic, N., Kaplan, D. L., Barron, A. E., & Fontaine, M. J. (2012). Enhanced function of pancreatic islets co-encapsulated with ECM proteins and mesenchymal stromal cells in a silk hydrogel. Biomaterials, 33(28), 6691–6697.

    Article  Google Scholar 

  147. Lee, S. H., Hao, E., Savinov, A. Y., Geron, I., Strongin, A. Y., & Itkin-Ansari, P. (2009). Human beta-cell precursors mature into functional insulin-producing cells in an immunoisolation device: Implications for diabetes cell therapies. Transplantation, 87(7), 983–991.

    Article  Google Scholar 

  148. Matveyenko, A. V., Georgia, S., Bhushan, A., & Butler, P. C. (2010). Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats. American Journal of Physiology-Endocrinology and Metabolism, 299(5), E713–E720.

    Article  Google Scholar 

  149. Colton, C. K. (2014). Oxygen supply to encapsulated therapeutic cells. Advanced Drug Delivery Reviews, 67–68, 93–110.

    Article  Google Scholar 

  150. Candiello, J., Singh, S. S., Task, K., Kumta, P. N., & Banerjee, I. (2013). Early differentiation patterning of mouse embryonic stem cells in response to variations in alginate substrate stiffness. Journal of Biological Engineering, 7(1), 9.

    Article  Google Scholar 

  151. Schulz, T. C. (2015). Concise review: Manufacturing of pancreatic endoderm cells for clinical trials in Type 1 diabetes. Stem Cells Translational Medicine, 4(8), 927–931.

    Article  Google Scholar 

  152. Pagliuca, F. W., Millman, J. R., Gürtler, M., Segel, M., Van Dervort, A., Ryu, J. H., … Melton, D. A. (2014). Generation of functional human pancreatic beta cells in vitro. Cell, 159(2), 428–439.

    Article  Google Scholar 

  153. Rezania, A., Bruin, J. E., Arora, P., Rubin, A., Batushansky, I., Asadi, A., … Yang, Y. H. C. (2014). Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nature Biotechnology, 32(11), 1121–1133.

    Article  Google Scholar 

  154. Russ, H. A., Parent, A. V., Ringler, J. J., Hennings, T. G., Nair, G. G., Shveygert, M., … Blelloch, R. (2015). Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. The EMBO Journal, 34(13), 1759–1772.

    Article  Google Scholar 

  155. Agulnick, A. D., Ambruzs, D. M., Moorman, M. A., Bhoumik, A., Cesario, R. M., Payne, J. K., …Kerr, J. (2015). Insulin-producing endocrine cells differentiated in vitro from human embryonic stem cells function in macroencapsulation devices in vivo. Stem Cells Translational Medicine, 4(10), 1214–1222.

    Article  Google Scholar 

  156. Tateishi, K., He, J., Taranova, O., Liang, G., D’Alessio, A. C., & Zhang, Y. (2008). Generation of insulin-secreting islet-like clusters from human skin fibroblasts. Journal of Biological Chemistry, 283(46), 31601–31607.

    Article  Google Scholar 

  157. Maehr, R., Chen, S., Snitow, M., Ludwig, T., Yagasaki, L., Goland, R., … Melton, D. A. (2009). Generation of pluripotent stem cells from patients with type 1 diabetes. Proceedings of the National Academy of Sciences, 106(37), 15768–15773.

    Article  Google Scholar 

  158. Lysy, P. A., Weir, G. C., & Bonner-Weir, S. (2012). Concise review: pancreas regeneration: Recent advances and perspectives. Stem Cells Translational Medicine, 1(2), 150–159.

    Article  Google Scholar 

  159. Noguchi, H., Xu, G., Matsumoto, S., Kaneto, H., Kobayashi, N., Bonner-Weir, S., & Hayashi, S. (2006). Induction of pancreatic stem/progenitor cells into insulin-producing cells by adenoviral-mediated gene transfer technology. Cell transplantation, 15(10), 929–938.

    Article  Google Scholar 

  160. Alberto Hayek, C.K., Brief review: Cell replacement therapies to treat type 1 diabetes mellitus. Clinical Diabetes and Endocrinology, 2(4).

    Google Scholar 

  161. Mason, M. N., & Mahoney, M. J. (2009). Selective beta-cell differentiation of dissociated embryonic pancreatic precursor cells cultured in synthetic polyethylene glycol hydrogels. Tissue Engineering Part A, 15(6), 1343–1352.

    Article  Google Scholar 

  162. D’Amour, K. A., Bang, A. G., Eliazer, S., Kelly, O. G., Agulnick, A. D., Smart, N. G., … Baetge, E. E. (2006). Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nature Biotechnology, 24(11), 1392–1401.

    Article  Google Scholar 

  163. Kroon, E., Martinson, L. A., Kadoya, K., Bang, A. G., Kelly, O. G., Eliazer, S., … Agulnick, A. D. (2008). Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nature Biotechnology, 26(4), 443–452.

    Article  Google Scholar 

  164. Chen, Y., Pan, F. C., Brandes, N., Afelik, S., Sölter, M., & Pieler, T. (2004). Retinoic acid signaling is essential for pancreas development and promotes endocrine at the expense of exocrine cell differentiation in Xenopus. Developmental Biology, 271(1), 144–160.

    Article  Google Scholar 

  165. Gomes, L. F., Lorente, S., Simon-Giavarotti, K. A., Areco, K. N., Araújo-Peres, C., & Videla, L. A. (2004). Tri-iodothyronine differentially induces Kupffer cell ED1/ED2 subpopulations. Molecular Aspects of Medicine, 25(1–2), 183–190.

    Article  Google Scholar 

  166. Schulz, T. C., Young, H. Y., Agulnick, A. D., Babin, M. J., Baetge, E. E., Bang, A. G., … Kadoya, K. (2012). A scalable system for production of functional pancreatic progenitors from human embryonic stem cells. PLoS One, 7(5), e37004.

    Article  Google Scholar 

  167. Shapiro, A. M., Nanji, S. A., & Lakey, J. R. (2003). Clinical islet transplant: Current and future directions towards tolerance. Immunological Reviews, 196, 219–236.

    Article  Google Scholar 

  168. Wang, T., Lacík, I., Brissová, M., Anilkumar, A. V., Prokop, A., Hunkeler, D., … Powers, A. C. (1997). An encapsulation system for the immunoisolation of pancreatic islets. Nature Biotechnology, 15(4), 358–362.

    Article  Google Scholar 

  169. Desai, T., & Shea, L. D. (2017). Advances in islet encapsulation technologies. Nature Reviews Drug Discovery, 16(5), 367.

    Article  Google Scholar 

  170. Brauker, J. H., Carr‐Brendel, V. E., Martinson, L. A., Crudele, J., Johnston, W. D., & Johnson, R. C. (1995). Neovascularization of synthetic membranes directed by membrane microarchitecture. Journal of Biomedical Materials Research Part A, 29(12), 1517–1524.

    Article  Google Scholar 

  171. Geller, R. L., Loudovaris, T., Neuenfeldt, S., Johnson, R. C., & Brauker, J. H. (1997). Use of an immunoisolation device for cell transplantation and tumor immunotherapy. Annals of the New York Academy of Sciences, 1997(831), 438–451.

    Google Scholar 

  172. Colton, C. K., & Avgoustiniatos, E. S. (1991). Bioengineering in development of the hybrid artificial pancreas. Journal of Biomechanical Engineering, 113(2), 152–170.

    Article  Google Scholar 

  173. Su, J., Hu, B. H., Lowe, W. L., Kaufman, D. B., & Messersmith, P. B. (2010). Anti-inflammatory peptide-functionalized hydrogels for insulin-secreting cell encapsulation. Biomaterials, 31(2), 308–314.

    Article  Google Scholar 

  174. Rafael, E., Wu, G. S., Hultenby, K., Tibell, A., & Wernerson, A. (2003). Improved survival of macroencapsulated islets of Langerhans by preimplantation of the immunoisolating device: A morphometric study. Cell Transplantation, 12(4), 407–412.

    Article  Google Scholar 

  175. Yakhnenko, I., Wong, W. K., Katkov, I. I., & Itkin-Ansari, P. (2012). Cryopreservation of human insulin expressing cells macro-encapsulated in a durable therapeutic immunoisolating device theracyte. Cryo Letters, 33(6), 518–531.

    Google Scholar 

  176. Rafael, E., Wernerson, A., Arner, P., Wu, G. S., & Tibell, A. (1999). In vivo evaluation of glucose permeability of an immunoisolation device intended for islet transplantation: A novel application of the microdialysis technique. Cell Transplantation, 8(3), 317–326.

    Article  Google Scholar 

  177. Kumagai-Braesch, M., Jacobson, S., Mori, H., Jia, X., Takahashi, T., Wernerson, A., … Tibell, A. (2013). The TheraCyte device protects against islet allograft rejection in immunized hosts. Cell Transplantation, 22(7), 1137–1146.

    Article  Google Scholar 

  178. ClinicalTrials.gov/beta/. (2016). ViaCyte: Three Year Follow-up Safety Study in Subjects Previously Implanted With VC-01™.

    Google Scholar 

Download references

Acknowledgements

We thank Dr. Kevin D’Amour for providing images from pre-clinical and clinical work at ViaCyte, San Diego, USA.

Author information

Authors and Affiliations

  1. Department of Bioengineering and Whitaker Institute of Biomedical Engineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0412, USA

    Isgard S. Hueck, Jane Frimodig, Pamela Itkin-Ansari & David A. Gough

  2. Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Isgard S. Hueck, Pamela Itkin-Ansari & David A. Gough

Authors
  1. Isgard S. Hueck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jane Frimodig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pamela Itkin-Ansari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David A. Gough
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isgard S. Hueck .

Editor information

Editors and Affiliations

  1. Institute for Neurophysiology, University of Cologne, Cologne, Germany

    Gerhard M. Artmann

  2. Institute for Bioengineering, Medical and Molecular Biology, University of Applied Sciences, Aachen, Campus Jülich, Germany

    Aysegül Artmann

  3. Department of Biology and Biotechnology, Kazakhstan National Academy of Natural Sciences, Al-Farabi Kazakh National University, Almaty, Kazakhstan

    Azhar A. Zhubanova

  4. Institute for Bioengineering, Cell- and Microbiology, University of Applied Sciences, Aachen, Campus Jülich, Germany

    Ilya Digel

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Hueck, I.S., Frimodig, J., Itkin-Ansari, P., Gough, D.A. (2018). Encapsulation of Stem Cells in Research and Therapy. In: Artmann, G., Artmann, A., Zhubanova, A., Digel, I. (eds) Biological, Physical and Technical Basics of Cell Engineering. Springer, Singapore. https://doi.org/10.1007/978-981-10-7904-7_2

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-7904-7_2

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-7903-0

  • Online ISBN: 978-981-10-7904-7

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation