In situ application of hydrogel-type fibrin-islet composite optimized for rapid glycemic control by subcutaneous xenogeneic porcine islet transplantation

Jung Sik Kim, Jong Hyung Lim, Hye Young Nam, Hyun Ju Lim, Jun Seop Shin, Jin Young Shin, Ju Hee Ryu, Kwangmeyung Kim, Ick Chan Kwon, Sang Man Jin, Hang Rae Kim, Sang Joon Kim, Chung Gyu Park

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28 Citations (Scopus)

Abstract

Maximum engraftment of transplanted islets is essential for the clinical application of a subcutaneous site. Significant barriers to the current approaches are associated with their low effectiveness, complexity and unproven biosafety. Here, we evaluated and optimized a fibrin-islet composite for effective glycemic control in a subcutaneous site whose environment is highly hypoxic due to low vascularization potential. In the setting of xenogeneic porcine islet transplantation into the subcutaneous space of a diabetic mouse, the in vivo islet functions were greatly affected by the concentrations of fibrinogen and thrombin. The optimized hydrogel-type fibrin remarkably reduced the marginal islet mass to approximately one tenth that of islets without fibrin. This marginal islet mass was comparable to that in the setting of the subcapsular space of the kidney, which is a highly vascularized organ. Highly vascularized structures were generated inside and on the outer surface of the grafts. A hydrogel-type fibrin-islet composite established early diabetic control within an average of 3.4 days after the transplantation. In the mechanistic studies, fibrin promoted local angiogenesis, enhanced islet viability and prevented fragmentation of islets into single cells. In conclusion, in situ application of hydrogel-type fibrin-islet composite may be a promising modality in the clinical success of subcutaneous islet transplantation.

Original languageEnglish
Pages (from-to)382-390
Number of pages9
JournalJournal of Controlled Release
Volume162
Issue number2
DOIs
Publication statusPublished - 2012 Sep 10

Keywords

  • Fibrin
  • Porcine islet
  • Subcutaneous islet transplantation
  • Xenotransplantation

ASJC Scopus subject areas

  • Pharmaceutical Science

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    Kim, J. S., Lim, J. H., Nam, H. Y., Lim, H. J., Shin, J. S., Shin, J. Y., Ryu, J. H., Kim, K., Kwon, I. C., Jin, S. M., Kim, H. R., Kim, S. J., & Park, C. G. (2012). In situ application of hydrogel-type fibrin-islet composite optimized for rapid glycemic control by subcutaneous xenogeneic porcine islet transplantation. Journal of Controlled Release, 162(2), 382-390. https://doi.org/10.1016/j.jconrel.2012.07.018