Particular Challenges in Microencapsulation of Insulin-Producing Cells for the Treatment of Diabetes Mellitus
Pp. 3-39 (37)
The ideal treatment for type 1 diabetes mellitus implies minute-to-minute modulations of insulin release according to the continuous variations of blood glucose. This can be accomplished by the transplantation of insulin-producing cells that are located in the pancreatic islets of Langerhans (islets). To avoid the use of potentially toxic immunosuppressive drugs, the cells may be entrapped within semi-permeable microcapsules. While several issues related to this task are similar to those found in other applications of cell microencapsulation, the present chapter emphasizes the challenges that are particular to the development of a bioartificial endocrine pancreas. In contrast to monocellular preparations used in other applications, islets are well organized cell cluster comprising 1500-3000 cells. However, the microcapsule membrane prevents transplanted islets from being re-vascularised. Therefore, oxygen supply depends upon diffusion only. Oxygen has to travel a relatively long distance to reach the cells located in the center of encapsulated islets. Central necrosis occurs, particularly in the largest islets. In contrast, dispersed single islet cells are very resistant to hypoxia but cannot function properly since they require cell-to-cell interactions. Thus, oxygen supply to encapsulated islet cells is crucial. Other issues that are particular to the bioartificial endocrine pancreas involve the number of islets to be transplanted, the rapid response of insulin release to variations of blood glucose levels, the limited supply of allogeneic islets from deceased donors and the implantation site. This chapter addresses all of these issues, as well as promising strategies that are being explored to overcome these hurdles.
Microencapsulation, diabetes, insulin, oxygenation, islet of Langerhans, aggregates, implantation, clinical trials, islet transplantation, bioengineering, immunosuppression, oxygen supply, hypoxia, xenografts.