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MSC-based Neo Islets: The Future of Long Term Diabetes Control?

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Review of  “Durable Control of Autoimmune Diabetes in Mice Achieved by Intraperitoneal Transplantation of “Neo-Islets,” Three-Dimensional Aggregates of Allogeneic Islet and “Mesenchymal Stem Cells”” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Recently described treatment strategies for type 1 diabetes mellitus (T1DM) have indicated that the administration of mesenchymal stem cells (MSCs) can improve pancreatic β-cell function when applied alone [1] or as part of a combinatorial treatment with islet cells [2, 3]. These improvements may arise from MSC-driven enhancements to islet cell survival, which can improve function, and elevated immunosuppressive activity, which protects islet cells and may abolish the need for potentially toxic anti-rejection drugs.

Now, researchers from the laboratory of Christof Westenfelder (University of Utah and VA Medical Centers, Salt Lake City, Utah, USA) have assessed whether three-dimensional Neo-Islets composed of culture-expanded allogeneic islet cells and large numbers of MSCs may represent the future for the treatment of T1DM in humans……and dogs [4]!

As a first step, Westenfelder et al. first tested the efficacy of intraperitoneal transplantation of Neo-Islets composed of approximately 50% MSCs and 50% islet cells in an immune-competent diabetic mouse model. Intraperitoneal transplantation aims to provide physiological insulin delivery and reduce the unwanted side effects associated with subcutaneously administered insulin. Encouragingly, mouse Neo-Islets engrafted into the peritoneum and began to produce insulin, which, in combination with the lack of any significant autoimmune response, returned blood sugar back to normal levels in a long-term study.

The authors then turned to the treatment of T1DM in mice with canine Neo-Islets, given both the prevalence of the disease in dogs and the possibility of garnering valuable information for envisioned clinical trials employing this large animal model. Excitingly, the transplantation of canine Neo-Islets provided the same benefits as mouse Neo-Islets, suggesting the overall efficacy of this treatment strategy. Additionally, the authors highlighted the fact that one donor pancreas provided for around 80 transplantable Neo Islets, thereby addressing the pressing problem of organ donor scarcity.

Neo Islets may be the future for the control of diabetes in the long term, and the authors of this exciting new study are working on several fronts to transfer this MSC-based strategy to humans. Future work aims to analyze the potential of human Neo Islets and provide an enhanced characterization of both the in vivo fate of MSC and the microcirculation of Neo Islets post-engraftment.

To discover all the future research into MSC-based Neo Islets, keep tuned to the Stem Cells Portal.

References

  1. Carlsson PO, Schwarcz E, Korsgren O, et al. Preserved beta-cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes 2015;64:587-592.
  2. Borg DJ, Weigelt M, Wilhelm C, et al. Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model. Diabetologia 2014;57:522-531.
  3. Cavallari G, Olivi E, Bianchi F, et al. Mesenchymal stem cells and islet cotransplantation in diabetic rats: improved islet graft revascularization and function by human adipose tissue-derived stem cells preconditioned with natural molecules. Cell Transplant 2012;21:2771-2781.
  4. Westenfelder C, Gooch A, Hu Z, et al. Durable Control of Autoimmune Diabetes in Mice Achieved by Intraperitoneal Transplantation of “Neo-Islets,” Three-Dimensional Aggregates of Allogeneic Islet and “Mesenchymal Stem Cells”. STEM CELLS Translational Medicine 2017;6:1631-1643.