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Retrieval of Microencapsulated Islet Grafts for Post-transplant Evaluation

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Cell Microencapsulation

Abstract

Microencapsulation of islets is a procedure used to immunoisolate islets in order to obviate the need for immunosuppression of islet transplant recipients. Although microencapsulated islets have routinely been transplanted in the peritoneal cavity, the ideal site for their engraftment remains to be determined. The omentum, a highly vascularized tissue, has been proposed as an alternative site for microencapsulated islet transplantation. An added benefit to the omentum is that implanted microcapsules can be easily retrieved for post-transplant evaluation. This chapter describes a collagenase-based procedure for the retrieval of microencapsulated islets following the harvest of omentum pouch site of transplantation.

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References

  1. White SA, Shaw JA, Sutherland DER (2009) Pancreas transplantation. Lancet 373(9677):1808–1817

    Article  CAS  Google Scholar 

  2. Hills CE, Brunskill NJ (2009) Cellular and physiological effects of C-peptide. Clin Sci (Lond) 116(7):565–574

    Article  CAS  Google Scholar 

  3. Opara EC, Mirmalek-Sani SH, Khanna O et al (2010) Design of a bioartificial pancreas. J Investig Med 58(7):831–837

    Article  Google Scholar 

  4. Berney T, Ricordi C (1999) Islet transplantation. Cell Transplant 8:461–464

    CAS  Google Scholar 

  5. Shapiro AMJ, Lakey JR, Ryan EA et al (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343:230–238

    Article  CAS  Google Scholar 

  6. Barton FB, Rickels MR, Alejandro R et al (2012) Improvements in outcomes of clinical islet transplantation: 1999-2010. Diabetes Care 35(7):1436–1445

    Article  CAS  Google Scholar 

  7. Lim F, Sun A (1980) Microencapsulated islets as bioartificial pancreas. Science 210(4472):908–910

    Article  CAS  Google Scholar 

  8. Prokop A (2001) Bioartificial pancreas: materials, devices function, and limitations. Diabetes Technol Ther 3(3):431–449

    Article  CAS  Google Scholar 

  9. O’Sullivan ES, Vegas A, Anderson DG et al (2011) Islets transplanted in immunoisolation devices: a review of the progress and the challenges that remain. Endocr Rev 32(6):827–844

    Article  Google Scholar 

  10. Opara EC, McQuilling JP, Farney AC (2013) Microencapsulation of islets for use in a bioartificial pancreas. In: Basu J, Ludlow JW (eds) Organ regeneration: methods and protocols. Humana Press, New York, pp 261–266

    Chapter  Google Scholar 

  11. Jain K, Yang H, Cai BR et al (1995) Retrievable, replaceable, macroencaspulated pancreatic islet xenografts. Long-term engraftment without immunosuppression. Transplantation 59(3):319–324

    Article  CAS  Google Scholar 

  12. Muthyala S, Raj VRR, Mohanty M et al (2011) The reversal of diabetes in rat model using mouse insulin producing cells – a combination approach of tissue engineering and macroencapsulation. Acta Biomater 7(5):2153–2162

    Article  CAS  Google Scholar 

  13. Opara EC, Kendall WF (2002) Immunoisolation techniques for islet cell transplantation. Expert Opin Biol Ther 2:503–511

    Article  Google Scholar 

  14. Weber LM, He J, Bradley B et al (2006) PEG-based hydrogels as an in vitro encapsulation platform for testing controlled beta-cell microenvironments. Acta Biomater 2(1):1–8

    Article  Google Scholar 

  15. Capretto L, Mazzitelli S, Luca G et al (2010) Preparation and characterization of polysaccharidic microbeads by a microfluidic technique: application to the encapsulation of Sertoli cells. Acta Biomater 6(2):429–435

    Article  CAS  Google Scholar 

  16. Rokstad AM, Brekke OL, Steinkjer B et al (2011) Alginate microbeads are complement compatible, in contrast to polycation containing microcapsules, as revealed in a human whole blood model. Acta Biomater 7(6):2566–2578

    Article  CAS  Google Scholar 

  17. Hall KK, Gattas-Asfura KM, Stabler CL (2011) Microencapsulation of islets within alginate/poly(ethylene glycol) gels cross-linked via Staudinger ligation. Acta Biomater 7(2):614–624

    Article  CAS  Google Scholar 

  18. Lee KY, Mooney DJ (2012) Alginate: properties and biomedical applications. Prog Polym Sci 37(1):106–126

    Article  CAS  Google Scholar 

  19. Tam SK, Bilodeau S, Dusseault J et al (2011) Biocompatibility and physicochemical characteristics of alginate-polycation microcapsules. Acta Biomater 7(4):1683–1692

    Article  CAS  Google Scholar 

  20. Soon-Shiong P, Heintz RE, Merideth N et al (1994) Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet 343(8903):950–951

    Article  CAS  Google Scholar 

  21. Calafiore R, Basta G, Luca G et al (2006) Microencapsulated pancreatic islet allograft into non-immunosuppressed patients with Type 1 diabetes. Diabetes Care 29(1):137–138

    Article  Google Scholar 

  22. Elliott RB, Escobar L, Tan PL et al (2007) Live encapsulated porcine islets from type 1 diabetic patient 9.5 yr. after xenotransplantation. Xenotransplantation 14(2):157–161

    Article  Google Scholar 

  23. Tuch BE, Keogh GW, Williams LJ et al (2009) Safety and viability of microencapsulated human islets transplanted into diabetic humans. Diabetes Care 32(10):1887–1889

    Article  CAS  Google Scholar 

  24. Living Cell Technologies. Clinical Trials 2012 Update. http://www.lctglobal.com/

  25. Sun Y, Ma X, Zhou D et al (1996) Normalization of diabetes in spontaneously diabetic Cynomolgus monkeys by xenografts of microencapsulated porcine islets without immunosuppression. J Clin Invest 98(6):1417–1422

    Article  CAS  Google Scholar 

  26. Wang T, Adcock J, Kuhtreiber W et al (2008) Successful allotransplantation of encapsulated islets in pancreatectomized canines for diabetic management without the use of immunosuppression. Transplantation 85(3):331–337

    Article  Google Scholar 

  27. Cui H, Tucker-Burden C, Cauffiel SM et al (2009) Long-term metabolic control of autoimmune diabetes in spontaneously diabetic non-obese diabetic mice by nonvascularized microencapsulated adult porcine islets. Transplantation 88(2):160–169

    Article  Google Scholar 

  28. Dufrane D, Goebbels RM, Saliez A et al (2006) Six month survival of microencapsulated pig islets and alginate biocompatibility in primates: proof of concept. Transplantation 81(9):1345–1353

    Article  Google Scholar 

  29. Kobayashi T, Aomatsu Y, Iwata H et al (2006) Survival of microencapsulated islets at 400 days post transplantation in the omental pouch of NOD mice. Cell Transplant 15(4):359–365

    Article  Google Scholar 

  30. Lacy PE, Kostianovsky M (1967) Method for the isolation of intact islets from the pancreas. Diabetes 16(1):35–39

    Article  CAS  Google Scholar 

  31. Field J, Farney A, Sutherland DE (1996) Improved islet isolation from rat pancreas using 35% bovine serum albumin in combination with Dextran gradient separation. Transplantation 61(10):1554–1556

    Article  CAS  Google Scholar 

  32. Tendulkar S, Mirmalek-Sani SH, Childers C et al (2012) A three-dimensional microfluidic approach to scaling up microencapsulation of cells. Biomed Microdevices 14(3):461–469

    Article  CAS  Google Scholar 

  33. Darrabie MD, Kendall WF, Opara EC (2005) Characteristics of poly-L-ornithine-coated alginate microcapsules. Biomaterials 26(34):6846–6852

    Article  CAS  Google Scholar 

  34. McQuilling JP, Arenas-Herrera J, Childers C et al (2011) New alginate microcapsule system for angiogenic protein delivery and immunoisolation of islets for transplantation in the rat omentum pouch. Transplant Proc 43(9):3262–3264

    Article  CAS  Google Scholar 

  35. Pareta R, McQuilling JP, Sivanandane S et al (2014) Long-term function of islets encapsulated in a redesigned alginate microcapsule construct in omentum pouches of immune-competent diabetic rats. Pancreas 43:605–613

    Article  CAS  Google Scholar 

  36. Lifson N, Lassa CV, Dixit PK (1985) Relation between blood flow and morphology in islet organ of rat pancreas. Am J Physiol 249(1):E43–E48

    CAS  Google Scholar 

  37. Jansson L, Hellerström C (1983) Stimulation by glucose of the blood flow to the pancreatic islets of the rat. Diabetologia 25(1):45–50

    Google Scholar 

  38. Dionne KE, Colton CK, Yarmush ML (1993) Effect of hypoxia on insulin secretion by isolated rat and canine islets of Langerhans. Diabetes 42(1):12–21

    Article  CAS  Google Scholar 

  39. Davalli AM, Scaglia L, Zangen DH et al (1996) Vulnerability of transplanted islets in the immediate post transplantation period; dynamic changes in structure and function. Diabetes 45(9):1161–1167

    Article  CAS  Google Scholar 

  40. Mendoza V, Klein D, Ichii H et al (2005) Protection of islets in culture by delivery of oxygen binding neuroglobin via protein transduction. Transplant Proc 37(1):237–240

    Article  CAS  Google Scholar 

  41. Jones GL, Juszczak MT, Hughes SJ et al (2007) Time course and quantification of pancreatic islet revascularization following intraportal transplantation. Cell Transplant 16(5):505–516

    Article  Google Scholar 

  42. De Vos P, Van Straaten JFM, Nieuwenhuizen AG et al (1999) Why do microencapsulated islet grafts fail in the absence of fibrotic overgrowth? Diabetes 48(7):1381–1388

    Article  Google Scholar 

  43. Ludwig B, Rotem A, Schmid J et al (2012) Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone agonist. Proc Natl Acad Sci U S A 109(13):5022–5027

    Article  CAS  Google Scholar 

  44. Pedraza E, Coronel MM, Fraker CA et al (2012) Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated oxygen generating biomaterials. Proc Natl Acad Sci U S A 109(11):4245–4250

    Article  CAS  Google Scholar 

  45. Goldsmith HS, Griffith AL, Kupferman A et al (1984) Lipid angiogenic factor from omentum. JAMA 252(15):2034–2036

    Article  CAS  Google Scholar 

  46. Herbert V, Lau KS, Gottlieb CW et al (1965) Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab 25(10):1375–1384

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to acknowledge financial support from the National Institutes of Health (RO1 DK080897) and the Vila Rosenfeld Estate, Greenville NC for the work in Dr. Opara’s laboratory at the Wake Forest Institute for Regenerative Medicine.

Also, research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) of the National Institutes of Health under award # T32EB014836. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Correspondence to Emmanuel C. Opara .

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McQuilling, J.P. et al. (2017). Retrieval of Microencapsulated Islet Grafts for Post-transplant Evaluation. In: Opara, E. (eds) Cell Microencapsulation. Methods in Molecular Biology, vol 1479. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6364-5_12

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  • DOI: https://doi.org/10.1007/978-1-4939-6364-5_12

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6362-1

  • Online ISBN: 978-1-4939-6364-5

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