Over the last two and a half decades, advancements in stem cell biology and immunology have improved the potential for cell therapy as a treatment for diabetes. Stem cells from different sources can be turned into the insulin-producing β cells lost in autoimmune attacks and returned to patients. While promising, lifelong immune suppression limits the ability to expand this option to patients. However, novel approaches may overcome this limitation.
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1) Many clinical trials currently use validated human embryonic stem cell lines. Researchers differentiate these precursors into β cells, which form clusters, or islets (1a). Recently, some groups explored encapsulating these cells into a device to limit the access of immune cells to the transplanted islets (1b). Otherwise, the islets are transplanted directly into the patient, most often through the main liver vein (1c).
2) Recently, researchers successfully used a patient’s own cells for diabetes cell therapy. The team isolated adipose stem cells (2a) and induced these into pluripotent stem cells (2b) before differentiating them into β cell islets (2c). They transplanted these islets into a subcutaneous region in the abdomen (2d).
3) Because current cell therapy applications for diabetes require immune suppression, researchers are exploring approaches to protect β cells from the immune system to minimize lifelong modulation requirements. A few examples of preclinical approaches are as follows: encasing the islets into gel matrices which reduces contact with immune cells (3a); genetically engineering β cells to express immune suppressive proteins or deleting proteins to block immune attack (3b); delivering islets alongside immune modulatory cells, like mesenchymal stem cells (3c); and developing biomaterials or devices to provide localized immune regulatory molecules in the area of the transplants (3d).
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