Diabetes islet cell transplants

Inogudii T, Battan R, Handler E, Sportsman JR, Heath W, King GL (1992) Preferential elevation of protein kinase C isoform pll and diacyl ycerol levels in the aorta and heart of diabetic rats differential reversibility to ycemic control by islet cell transplantation. Proc Natl Acad Sd USA 89 11059-11063... 

The islet cells transplanted into humans are obtained from pancreatic tissue of deceased human donors (Figure 8.9). Implantation of these cells in recipients displaying a competent immune system would, at best, be of transient therapeutic benefit. The ensuing immune response would quickly destroy the foreign cells. Studies conducted thus far in humans have utilized diabetic patients who have received kidney transplants, as these are already subject to immunosuppressive therapy. However, a major stumbling block to the widespread adoption of this therapeutic approach is, predictably, the requirement to induce concurrent immune suppression. 

Kapturczak, M. H., Flotte, T. and Atkinson, M. A. (2001). Adeno-associated virus (AAV) as a vehicle for therapeutic gene delivery Improvements in vector design and viral production enhance potential to prolong graft survival in pancreatic islet cell transplantation for the reversal of type 1 diabetes. Curr. Mol. Med. 1, 245-258. 

Lacy P. Status of islet cell transplantation. Diabetes Rev 1993 1 76-92. 

Cell transplantation has shown promise as a method for treating serious diseases. Various kinds of pluripotent stem cells have been developed or identified, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs). Moreover, the differentiation of stem cells to functional cells has been extensively studied. Previous studies have demonstrated that the transplantation of islet of Langerhans cells (islets) could successfully treat type 1 diabetes. Islets are insulin-secreting cells found in the pancreas. Over 200 patients... 

Initial experiments in the 1970s using inbred strains of rats illustrated the feasibility of this approach. Insulin-producing pancreatic islet cells donated by one set of rats were transplanted into other rats of the same strain, first made diabetic by injection with drugs such as streptozotocin, which destroy the pancreatic B cells. 

Smith, D. K., Korbutt, G. S., Suarez-Pinzon, W. L., Kao, D., Rajotte, R. V. and Elliott, J. F. (1997). Interleukin-4 or interleukin-10 expressed from adenovirus-transduced syngeneic islet grafts fails to prevent beta cell destruction in diabetic NOD mice. Transplantation 64, 1040-1049. 

Today, with the exception of bone marrow for hematopoietic reconstitution, therapeutic cellular transplantation is an emerging technology. In recent years novel approaches in the potential restoration of function through cellular transplantation have included the use of fetal human or xenogeneic neural tissue for Parkinson s disease, ectopically implanted pancreatic islets for diabetes, Schwann cells and olfactory ensheathing glia for spinal cord injury, encapsulated chromaffin cells for pain, and various types of stem cells for the treatment of diabetes, cardiac disease, and central nervous system injuries or disease [2], There have also been trials of encapsulated cells to provide enzymes that either remove toxic products or provide activation of prodrugs to therapeutics, usually anticancer derivatives. 

Classification of diabetes mellitus Assessment of p-ceU activity Obtain insurance coverage for insulin pump Monitoring therapy Pancreatectomy Transplant (pancreas-islet cell)... 

Immunoisolation may also have an advantage in preventing the autoimmune destruction of the transplanted islets (27) by separating them from the host (T-cells or autoantibodies) by the permselective membrane. Although the detailed mechanism of islet cell damage is unknown, evidence from spontaneously diabetic BB rats indicates that the rapid failure of islet transplants, even in twins (28), may be due to a recurrence of autoimmune disease rather than the conventional transplant rejection phenomenon (29). 

Further research examining the transplantation of pancreatic islet cells identifies this approach aimed at curing type 1 diabetes. Unfortunately, the loss of cell function following transplantation presents a major issue. Macroencapsulation of cells in order to isolate and protect them from immune responses have proven unsuccessful, resulting in hypoxic death due to poor diffusion of essential molecules. Nanoencapsulation has been shown to allow for sufficient molecular permeability without significant... 

Dieterle, C., Brendel, M. D., Seissler, J., Eckhard, M., Bretzel, R. G., and Landgraf, R. 2006. Therapy of diabetes mellitus. Pancreas transplantation, islet transplantation, stem cell and gene therapy. Internist (Berlin)... 

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