Successful Islet Transplant… Scaffolds, Stem Cells, and More
By: Mari Yamamoto
Clinical application of islet transplantation is often limited. Before transplant, it’s limited simply by the lack of viable donors. After transplant, it’s limited by the risk of rejection and the need for immunosuppression. Much of the recent research around islet transplants seek a way to overcome these major obstacles. Let’s take a look at some of these technologies.
A Positive Bioscaffold
This study describes a new cationic co-polymeric biomaterial, used as a bioscaffold for islet cells. The protonation of the scaffold allows it to interact with the negatively charged membranes of the islet cells, and these electrostatic interactions are crucial for the retention of the islet cells and the creation of a stable, pancreas-like structure.
So what were the results of using the seeded scaffold?
- Ability to maintain the islet microenvironment
- Long-term survival of the graft in diabetic NOD and STZ mouse models with neovascularization
- Elevated insulin levels and reduced blood glucose
Stem Cell-derived Islets
Another approach to extend the applicability of transplantation is the encapsulation of stem cell-derived islets. Here, researchers used conformal coating for these islets, looking to avoid the problems that come with traditionally thicker microencapsulation. The thinner conformal coating means better oxygen access, reducing the risk of hypoxia-induced islet death. The conformal-coated SC islets proved to function at similar levels to unencapsulated SC islets, and both groups of islets were able to reverse diabetes in mice.
Researchers in Taiwan used bone marrow stem cells to construct donor chimerism, where all bone marrow and blood cells come from donor origin. They studied the effect on the survival of subcutaneously transplanted allogeneic islets in diabetic mice. Only complete, full donor chimerism was associated with both successful engraftment of the transplants and the restoration of normal blood glucose levels – without the use of immunosuppressants.
Takeaway: Islet transplantation has a lot of promise in treating diabetes, but its application is limited. These studies seek to expand this application, and find solutions to obstacles such as the body’s immune response.
- Elizondo, D.M., Brandy, N.Z.D., da Silva, R.L.L. et al. Pancreatic islets seeded in a novel bioscaffold forms an organoid to rescue insulin production and reverse hyperglycemia in models of type 1 diabetes. Sci Rep 10, 4362 (2020). https://doi.org/10.1038/s41598-020-60947-x
- Stock, A. A., Manzoli, V., De Toni, T., Abreu, M. M., Poh, Y. C., Ye, L., Roose, A., Pagliuca, F. W., Thanos, C., Ricordi, C., & Tomei, A. A. (2020). Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes. Stem cell reports, 14(1), 91–104. https://doi.org/10.1016/j.stemcr.2019.11.004
- Hsu, B. R., Fu, S. H., & Wang, A. (2017). Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment. International journal of endocrinology, 2017, 7057852. https://doi.org/10.1155/2017/7057852