Skip to main content
Log in

Optimization of pancreatic islet spheroid using various concave patterned-films

  • Articles
  • Published:
Macromolecular Research Aims and scope Submit manuscript

Abstract

In the pancreatic islet transplantation for curing diabetes mellitus, reaggregation of pancreatic islet single cells for making ‘islet spheroid’ is considered as a useful strategy in terms of islet viability and gene delivery into islet. However, during aggregation of islet spheroid, their insulin secretion pattern was not recovered to that of intact islets. We have developed a new cell-culture system using poly(dimethylsiloxane) (PDMS)-based concave-patterned film for aggregating islet spheroid. Here we optimized the effective formation of islets spheroid by using the concave-patterned film with different microwell diameter (300, 500, and 700-μm). Aggregated islet spheroids in different concave microwells showed same morphology with a limited size range and diameter dependency of microwell, which was similar to that of intact islet. However, islet spheroid in flat-bottomed dish (control) showed random aggregation with broad size distribution. Interestingly, insulin secretion pattern of islet spheroids in 300 and 500-μm concave patterned-film was same to that of intact islets, which was caused by the improved cell-to-cell interaction that was confirmed by electron microscope and strong phalloidin immunostain. However, islet spheroids in concave patterned-film with 700-μm diameter and flat-dish did not show normal insulin secretion in accordance with different glucose concentration, which might be caused by weak cell-to-cell interaction. On the other hand, the viability of islet spheroids in concave patterned-film was not affected during cultivation due to biocompatibility of PDMS polymer. Collectively, we demonstrated that PDMS-based concave-patterned film could be used for designing islet spheroids with improved cellular functionality and size uniformity to cure diabetes mellitus.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. A. M. Shapiro, C. Ricordi, B. J. Hering, H. Auchincloss, R. Lindblad, R. P. Robertson, A. Secchi, M. D. Brendel, T. Berney, D. C. Brennan, E. Cagliero, R. Alejandro, E. A. Ryan, B. DiMercurio, P. Morel, K. S. Polonsky, J. A. Reems, R. G. Bretzel, F. Bertuzzi, T. Froud, R. Kandaswamy, D. E. Sutherland, G. Eisenbarth, M. Segal, J. Preiksaitis, G. S. Korbutt, F. B. Barton, L. Viviano, V. Seyfert-Margolis, J. Bluestone, and J. R. Lakey, New Engl. J. Med., 355, 1318 (2006).

    Article  CAS  Google Scholar 

  2. R. M. Leach and D. F. Treacher, BMJ, 317, 1370 (1998).

    Article  CAS  Google Scholar 

  3. P. O. Carlsson, F. Palm, A. Andersson, and P. Liss, Diabetes, 50, 489 (2001).

    Article  CAS  Google Scholar 

  4. I. F. Tannock, Br. J. Radiol., 45, 515 (1972).

    Article  CAS  Google Scholar 

  5. A. M. Davalli, Y. Ogawa, C. Ricordi, D. W. Scharp, S. Bonner-Weir, and G. C. Weir, Transplantation, 59, 817 (1995).

    CAS  Google Scholar 

  6. R. Lehmann, R. A. Zuellig, P. Kugelmeier, P. B. Baenninger, W. Moritz, A. Perren, P. A. Clavien, M. Weber, and G. A. Spinas, Diabetes, 56, 594 (2007).

    Article  CAS  Google Scholar 

  7. R. R. MacGregor, S. J. Williams, P. Y. Tong, K. Kover, W. V. Moore, and L. Stehno-Bittel, Am J. Physiol. Endocrinol. Metab., 290, E771 (2006).

    Article  CAS  Google Scholar 

  8. A. L. Gainer, G. S. Korbutt, R. V. Rajotte, G. L. Warnock, and J. F. Elliott, Transplantation, 63, 1017 (1997).

    Article  CAS  Google Scholar 

  9. K. Cheng, D. Fraga, C. Zhang, M. Kotb, A. O. Gaber, R. V. Guntaka, and R. I. Mahato, Gene Therapy, 11, 1105 (2004).

    Article  CAS  Google Scholar 

  10. A. S. Narang and R. I. Mahato, Pharmacol. Rev., 58, 194 (2006).

    Article  CAS  Google Scholar 

  11. I. Konstantinova, G. Nikolova, M. Ohara-Imaizumi, P. Meda, T. Kucera, K. Zarbalis, W. Wurst, S. Nagamatsu, and E. Lammert, Cell, 129, 359 (2007).

    Article  CAS  Google Scholar 

  12. A. Lim, S. H. Park, J. W. Sohn, J. H. Jeon, J. H. Park, D. K. Song, S. H. Lee, and W. K. Ho, Diabetes, 58, 2813 (2009).

    Article  CAS  Google Scholar 

  13. J. W. Hwang, B. R. Lee, M. J. Jung, H. S. Jung, Y. H. Hwang, M. J. Kim, S. H. Lee, and D. Y. Lee, Macromol. Res., 19, 1320 (2011).

    Article  CAS  Google Scholar 

  14. J. Y. Park, D. H. Lee, E. J. Lee, and S. H. Lee, Lab Chip, 9, 2043 (2009).

    Article  CAS  Google Scholar 

  15. Y. Y. Choi, B. G. Chung, D. H. Lee, A. Khademhosseini, J. H. Kim, and S. H. Lee, Biomaterials, 31, 4296 (2010).

    Article  CAS  Google Scholar 

  16. S. F. Wong, D. Y. No, Y. Y. Choi, D. S. Kim, B. G. Chung, and S. H. Lee, Biomaterials, 32, 8087 (2011).

    Article  CAS  Google Scholar 

  17. D. H. Lee, J. Y. Park, E. J. Lee, Y. Y. Choi, G. H. Kwon, B. M. Kim, and S. H. Lee, Biomed. Microdevices, 12, 49 (2010).

    Article  CAS  Google Scholar 

  18. P. A. Halban, S. L. Powers, K. L. George, and S. Bonner-Weir, Diabetes, 36, 783 (1987).

    Article  CAS  Google Scholar 

  19. M. A. Schwartz and E. J. Luna, J. Cell Biol., 102, 2067 (1986).

    Article  CAS  Google Scholar 

  20. R. M. Hernandez, G. G. Wescott, M. W. Mayhew, M. A. McJilton, and D. M. Terrian, J. Cell Biochem., 83, 532 (2001).

    Article  CAS  Google Scholar 

  21. S. H. Lee, D. H. Kang, H. N. Kim, and K. Y. Suh, Lab Chip, 10, 3300 (2010).

    Article  CAS  Google Scholar 

  22. T. G. van Kooten, J. F. Whitesides, and A. von Recum, J. Biomed. Mater. Res., 43, 1 (1998).

    Article  Google Scholar 

  23. J. A. Cooper, J. Cell. Biol., 105, 1473 (1987).

    Article  CAS  Google Scholar 

  24. H. C. Cable, A. El-Mansoury, and N. G. Morgan, Biochem. J., 307(Pt 1), 169 (1995).

    CAS  Google Scholar 

  25. E. S. O’sullivan, A. S. Johnson, A. Omer, J. Hollister-Lock, S. Bonner-Weir, C. K. Colton, and G. C. Weir, Diabetologia, 53, 937 (2010).

    Article  Google Scholar 

  26. D. Y. Lee, S. J. Park, J. H. Nam, and Y. Byun, J. Biomater. Sci. Polym. Ed., 19, 441 (2008).

    Article  CAS  Google Scholar 

  27. G. Cavallari, R. A. Zuellig, R. Lehmann, M. Weber, and W. Moritz, Transplant. Proc., 39, 2018 (2007).

    Article  CAS  Google Scholar 

  28. S. G. Matta, J. D. Wobken, F. G. Williams, and G. E. Bauer, Pancreas, 9, 439 (1994).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dong Yun Lee.

Additional information

Equally contributed in this study as first author.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hwang, J.W., Kim, M.J., Kim, H.J. et al. Optimization of pancreatic islet spheroid using various concave patterned-films. Macromol. Res. 20, 1264–1270 (2012). https://doi.org/10.1007/s13233-012-0189-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13233-012-0189-9

Keywords

Navigation