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Cell Encapsulation Boosts Stem Cell Therapy for Type 1 Diabetes

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Review of “Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice” from Nature Medicine by Stuart P. Atkinson

The production of glucose-responsive, insulin-producing -cells from human embryonic stem cells (ESCs) is a promising strategy for the treatment of type 1 diabetes [1]. Transplantation of such cells into human patients may, however, elicit an unwanted immune response, or require that the patient undergoes life-long immunosuppressive therapy. But what if there was a way to mitigate this immune response? 

The laboratory of Daniel G Anderson (MIT, USA) believe they have found a potential strategy – the encapsulation of stem cell-derived -cells (SC- cells) in triazole–thiomorpholine dioxide (TMTD)-derivatized alginate, a seaweed-derived product [2]. Their new study, published in Nature Medicine, reports that this strategy not only mitigated the detrimental immune response but also induced long-term glycemic correction without the need for immunosuppression [3].

The study employed diabetic streptozotocin (STZ)-treated immune-competent C57BL/6J mice as a model system, and first assessed the ability of encapsulated SC-β cells to induce glycemic correction. At 90 days post transplantation, the authors found that only TMTD alginate-encapsulated cells could provide sustained nor-moglycemia when compared to non-encapsulated cells and cells encapsulated in alginate only. Furthermore, assessment of various cell formulations at 14 days post-transplantation found that TMTD alginate–encapsulated SC-β cells attracted significantly lower numbers of macrophages, neutrophils, B cells and CD8+ T cells, even though the study did not employ any form of immunosuppressive therapy. Assessments of TMTD alginate spheres over days 80-90 also suggested that this formulation provoked significantly less fibrotic responses when compared to alginate encapsulation.

But what about later time points? The authors also assessed glycemic correction up to 174 days (at which point mice display complications related to STZ treatment) and, excitingly, they found that the transplanted mice maintained glycemic correction throughout this time. Additionally, they saw no fibrotic overgrowth with minimal deposition of collagen and cells on the capsule surface while the SC-β cells inside survived and maintained their differentiation state.

The authors state, to their knowledge, that this is not only the first evidence for long-term glycemic correction achieved by the transplantation of embryonic stem cell-derived β cells but also represents the longest duration of stable normoglycemia achieved in an immune-competent rodent model. This should hopefully propel this treatment strategy towards human studies and lead to the generation of an effective therapeutic avenue for the treatment of type 1 diabetes. Sweet success!

References

  1. Pagliuca FW, Millman JR, Gurtler M, et al. Generation of functional human pancreatic beta cells in vitro. Cell 2014;159:428-439.
  2. Vegas AJ, Veiseh O, Doloff JC, et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat Biotechnol 2016;34:345-352.
  3. Vegas AJ, Veiseh O, Gurtler M, et al. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat Med 2016;22:306-311.