Building Biomimetic Potency Tests for Islet Transplantation

Author:

Glieberman Aaron L.1ORCID,Pope Benjamin D.1ORCID,Melton Douglas A.23,Parker Kevin Kit13ORCID

Affiliation:

1. Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA

2. Harvard Department of Stem Cell and Regenerative Biology, Cambridge, MA

3. Harvard Stem Cell Institute, Cambridge, MA

Abstract

Diabetes is a disease of insulin insufficiency, requiring many to rely on exogenous insulin with constant monitoring to avoid a fatal outcome. Islet transplantation is a recent therapy that can provide insulin independence, but the procedure is still limited by both the availability of human islets and reliable tests to assess their function. While stem cell technologies are poised to fill the shortage of transplantable cells, better methods are still needed for predicting transplantation outcome. To ensure islet quality, we propose that the next generation of islet potency tests should be biomimetic systems that match glucose stimulation dynamics and cell microenvironmental preferences and rapidly assess conditional and continuous insulin secretion with minimal manual handing. Here, we review the current approaches for islet potency testing and outline technologies and methods that can be used to arrive at a more predictive potency test that tracks islet secretory capacity in a relevant context. With the development of potency tests that can report on islet secretion dynamics in a context relevant to their intended function, islet transplantation can expand into a more widely accessible and reliable treatment option for individuals with diabetes.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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