Evaluating a Library of Modified Alginates to Reverse Diabetes Through Islet Encapsulation

Tuesday, October 18, 2011: 4:35 PM
L100 F (Minneapolis Convention Center)
Kaitlin M. Bratlie, Arturo J. Vegas, Thema M. Vietti, Alan Chiu, Nimit Dholakia, Robert Langer and Daniel G. Anderson, Chemical Engineering, MIT, Cambridge, MA

  According to the American Diabetes Association, diabetes affects over 20.8 million people in the United States or about 7% of the population.  Current treatments involve daily injection of insulin from recombinant human or animal sources.  Controlling diabetes has proven difficult since regulation of insulin secreted by the β-cells of the pancreatic islets in response to blood glucose is a highly dynamic process.  We are particularly interested in developing materials for reducing host-responses for polymer encapsulated insulin producing β-cells, which has potential as a type I diabetes therapeutic.  Encapsulating β-cells in polymers to evade host-responses was first proposed by Lim & Sun1 using alginate, a natural polymer derived from seaweed. Elliott et al.2 found that alginate encapsulated porcine islets remained viable 9.5 years after transplantation.  However, the alginate particles were encapsulated in fibrous tissue, resulting in poor diffusion of insulin into the patient’s blood stream.  Based on these findings, our approach has been to develop a library of modified alginates for encapsulating β-cells that are more biocompatible than existing alginate. 

  In assessing biocompatibility, our goal is to develop in vivo fluorescence imaging for assessing the host-response to libraries of implanted biomaterials to determine which chemical functionalities mitigate the foreign body response.  We have developed a method for imaging the foreign body response through cathepsin activity imaging.  Through this imaging platform, we are able to assess early time-point responses to implanted materials.  We have examined a 1000 member library based on alginate for encapsulating β-cells.  Histological analysis of these implanted materials complements early time point imaging in assessing host responses.

  Novel alginates identified as biocompatible through in vivo imaging and histology were used to encapsulate β-cells isolated from rats and were implanted into diabetic mice.  Several polymers were found to be as efficacious as unmodified alginate in stabilizing blood glucose levels for periods longer than one month.  Future plans in this work include developing a more apt mouse model to differentiate between unmodified and modified alginates.

 References

1.   Lim, F.; Sun, A. M., Microencapsulated islets as bioartificial endocrine pancreas. Science 1980, 210, 908-910.

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

 



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