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The effect of two different polyethylene glycol (PEG) derivatives on the immunological response of PEG grafted pancreatic islets

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Abstract

Islet transplantation is one of the promising ways to treat diabetes. To reduce the immune system response, several methods have been developed, a novel one being the grafting of methoxy polyethylene glycol (mPEG) derivatives onto collagen capsules of islets. In this study, the effects of the first and second generations of activated mPEG on the immunological response of polyethylene glycol (PEG) grafted pancreatic islets were studied. mPEG-Succinimidyl carbonate (mPEG-SC) and mPEG-succinimidyl propionic acid (mPEG-SPA) (with nominal molecular weight 5 kDa), typical of the first and second generations of activated mPEG, were selected, respectively. Both activated mPEGs did not affect the morphology, viability, or functionality of PEGylated islets compared to free islets (naked islets). The amount of IL-2 secreted from lymphocytes co-cultured with mPEG-SPA grafted islets (131.83 ± 15.28 pg/ml) was not significantly different from that with mPEG-SC grafted islets (156.09 ± 27.94 pg/ml). These results indicated that both mPEG-SC and mPEG-SPA had the same effect for camouflaging Langerhans islets, but the former is more suitable due to its easier synthesis process.

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References

  1. Alberti KG, Aschner P, Groop L. Part1: diagnosis and classification of diabetes mellitus: WHO consultation. Geneve: World Health Organization, Department of Noncommunicable Disease Surveillance; 1999.

  2. Graham RM. Cyclosporine: mechanisms of action and toxicity. Clevel Clin J Med. 1994;61:308–13.

    CAS  Google Scholar 

  3. Neithammer D, Deschner JK, Dannecker GE. Side effect of long term immunosuppression versus morbidity in autologous stem cell rescue: striking the balance. Rheumatology. 1999;38:747–50.

    Article  Google Scholar 

  4. Shapiro AMJ, Ryan EA, Lakey JRT. Pancreatic islet transplantation in the treatment of diabetes mellitus. Best Pract Res Clin Endocrinol Metab. 2001;15:241–62.

    Article  CAS  PubMed  Google Scholar 

  5. Beck J, Angus R, Madsen B, Britt D, Vernon B, Nguyen KT. Islet encapsulation: strategies to enhance islet cell functions. Tissue Eng. 2007;13:589–99.

    Article  CAS  PubMed  Google Scholar 

  6. Prokop A. Bioartificial pancreas: materials, devices, function, and limitations. Diabetes Technol Ther. 2001;3:431–49.

    Article  CAS  PubMed  Google Scholar 

  7. Lim F, Sun AM. Microencapsulated islets as bioartificial endocrine pancreas. Science. 1980;210:908–10.

    Article  CAS  PubMed  Google Scholar 

  8. Silva AI, de Matos A, Brons IG, Mateus M. An overview on the development of a bio-artificial pancreas as a treatment of insulin-dependent diabetes mellitus. Med Res Rev. 2006;26:181–222.

    Article  CAS  PubMed  Google Scholar 

  9. Veronese FM, Mero A, Pasut Gianfranco. Protein PEGylation, basic science and biological applications. In: Veronese FM, editor. PEGylated protein drugs: basic science and clinical applications. Basel: Birkhäuser Verlag Publication; 2009. p. 11–31.

    Chapter  Google Scholar 

  10. Hashemi Najafabadi S, Vasheghani Farahani E, Shojaosadati SA, Armstrong JK, Moin M, Pourpak Z. A method to optimize PEG-coating of red blood cells. Bioconjugate Chem. 2006;17:1288–93.

    Article  CAS  Google Scholar 

  11. Li RH. Materials for immunoisolated cell transplantation. Adv Drug Del Rev. 1998;33:87–109.

    Article  Google Scholar 

  12. Koswolski A, Harris JM. Protein pegylation. New life for an old technology. In: Yui N, Jeong SY, editors. Biomaterials and drug delivery toward new mellenium. Seoul: Han Rim Won Publishing Co.; 2000. p. 63–74.

  13. Lee DY, Yang K, Lee S, Chae SY, Kim KW, Lee MK, Han DJ, Byun Y. Optimization of monomethoxypolyethylene glycol grafting on the pancreatic islet capsules. J Biomed Mater Res. 2002;62:372–7.

    Article  CAS  PubMed  Google Scholar 

  14. Terumara Y, Iwata H. Surface modification of islets with PEG-lipid for improvment of graft survival in intraportal transplantation. Transplantation. 2009;88:624–30.

    Article  Google Scholar 

  15. Heman S, Hooftman G, Schacht E. Poly(ethylene glycol) with reactive endgroups: I. Modification of proteins. J Bioact Compat Polym. 1995;10:145–87.

    Google Scholar 

  16. Roberts MJ, Harris JM. Attachment of degradable poly(ethyleneglycol) to proteins has the potential to increase therapeutic efficacy. J Pharm Sci. 1998;87:1440–5.

    Article  CAS  PubMed  Google Scholar 

  17. Harris JM, Kozlowski A. Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications. 1997. US patent 5672662.

  18. Jang JY, Lee DY, Park SJ, Byun Y. Immune reactions of lymphocytes and macrophages against PEG-grafted pancreatic islets. Biomaterials. 2004;25:3663–9.

    Article  CAS  PubMed  Google Scholar 

  19. Le Y, Scott MD. Immnunocamouflage: the biophysical basis of immunoprotection by grafted methoxypoly(ethylene glycol) (mPEG).Acta Biomater. 2010. doi:10.1016/j.actbio.2010.01.031.

  20. Miron T, Wilcheck MA. A simplified method for preparation of succinimidyl carbonate polyethylene glycol for coupling to proteins. Bioconjugate Chem. 1993;4:568–9.

    Article  CAS  Google Scholar 

  21. Rosen P, Kwang N. Novel monofunctional polyethylene glycol aldehydes. 2003. US patent no. 20030153694A1.

  22. Lacy PE, Kostinovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes. 1967;16:35–9.

    CAS  PubMed  Google Scholar 

  23. Bank HL. Assessment of islet cell viability using fluorescent dyes. Diabetologia. 1987;30:812–6.

    Article  CAS  PubMed  Google Scholar 

  24. Lee DY, Park SJ, Nam HJ, Byun Y. A combination therapy of PEGylation and immunosuppressive agent for successful islet transplantation. J Control Release. 2006;110:290–5.

    Article  CAS  PubMed  Google Scholar 

  25. Lee DY, Park SJ, Nam HJ, Byun Y. A new strategy toward improving immunoprotection in cell therapy for diabetes mellitus: long-functioning PEGylated islets in vivo. Tissue Eng. 2006;12:615–23.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grant no. S88P/3/1518 from the Ministry of Health and Medical Education, the Deputy of the Research and Food and Drugs Department, Islamic Republic of Iran.

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Authors and Affiliations

  1. Biotechnology Group, Department of Chemical Engineering, Faculty of Engineering, Tarbiat Modares University, P.O. Box 14115-143, Tehran, Iran

    Hamideh Aghajani-Lazarjani, Ebrahim Vasheghani-Farahani, Seyed Abbas Shojaosadati & Sameereh Hashemi-Najafabadi

  2. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Saleh Zahediasl

  3. Department of Anatomy, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Taki Tiraihi

  4. Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Fatemeh Atyabi

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  1. Hamideh Aghajani-Lazarjani
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  2. Ebrahim Vasheghani-Farahani
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  3. Seyed Abbas Shojaosadati
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  4. Sameereh Hashemi-Najafabadi
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  6. Taki Tiraihi
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Correspondence to Ebrahim Vasheghani-Farahani.

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Aghajani-Lazarjani, H., Vasheghani-Farahani, E., Shojaosadati, S.A. et al. The effect of two different polyethylene glycol (PEG) derivatives on the immunological response of PEG grafted pancreatic islets. J Artif Organs 13, 218–224 (2010). https://doi.org/10.1007/s10047-010-0525-9

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