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Statistical approaches and software for clustering islet cell functional heterogeneity.

ABSTRACT: Worldwide efforts are underway to replace or repair lost or dysfunctional pancreatic ?-cells to cure diabetes. However, it is unclear what the final product of these efforts should be, as ?-cells are thought to be heterogeneous. To enable the analysis of ?-cell heterogeneity in an unbiased and quantitative way, we developed model-free and model-based statistical clustering approaches, and created new software called TraceCluster. Using an example data set, we illustrate the utility of these approaches by clustering dynamic intracellular Ca(2+) responses to high glucose in ?300 simultaneously imaged single islet cells. Using feature extraction from the Ca(2+) traces on this reference data set, we identified 2 distinct populations of cells with ?-like responses to glucose. To the best of our knowledge, this report represents the first unbiased cluster-based analysis of human ?-cell functional heterogeneity of simultaneous recordings. We hope that the approaches and tools described here will be helpful for those studying heterogeneity in primary islet cells, as well as excitable cells derived from embryonic stem cells or induced pluripotent cells.

SUBMITTER: Wills QF

PROVIDER: S-EPMC4878268 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Statistical approaches and software for clustering islet cell functional heterogeneity.

Wills Quin F QF Boothe Tobias T Asadi Ali A Ao Ziliang Z Warnock Garth L GL Kieffer Timothy J TJ Johnson James D JD

Islets 20160301 2

Worldwide efforts are underway to replace or repair lost or dysfunctional pancreatic β-cells to cure diabetes. However, it is unclear what the final product of these efforts should be, as β-cells are thought to be heterogeneous. To enable the analysis of β-cell heterogeneity in an unbiased and quantitative way, we developed model-free and model-based statistical clustering approaches, and created new software called TraceCluster. Using an example data set, we illustrate the utility of these appr ...[more]

PMID: 26909740

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Project description:Immunoisolation of pancreatic islets is a technology in which islets are encapsulated in semipermeable but immunoprotective polymeric membranes. The technology allows for successful transplantation of insulin-producing cells in the absence of immunosuppression. Different approaches of immunoisolation are currently under development. These approaches involve intravascular devices that are connected to the bloodstream and extravascular devices that can be distinguished in micro- and macrocapsules and are usually implanted in the peritoneal cavity or under the skin. The technology has been subject of intense fundamental research in the past decade. It has co-evolved with novel replenishable cell sources for cure of diseases such as Type 1 Diabetes Mellitus that need to be protected for the host immune system. Although the devices have shown significant success in animal models and even in human safety studies most technologies still suffer from undesired tissue responses in the host. Here we review the past and current approaches to modulate and reduce tissue responses against extravascular cell-containing micro- and macrocapsules with a focus on rational choices for polymer (combinations). Choices for polymers but also choices for crosslinking agents that induce more stable and biocompatible capsules are discussed. Combining beneficial properties of molecules in diblock polymers or application of these molecules or other anti-biofouling molecules have been reviewed. Emerging are also the principles of polymer brushes that prevent protein and cell-adhesion. Recently also immunomodulating biomaterials that bind to specific immune receptors have entered the field. Several natural and synthetic polymers and even combinations of these polymers have demonstrated significant improvement in outcomes of encapsulated grafts. Adequate polymeric surface properties have been shown to be essential but how the surface should be composed to avoid host responses remains to be identified. Current insight is that optimal biocompatible devices can be created which raises optimism that immunoisolating devices can be created that allows for long term survival of encapsulated replenishable insulin-producing cell sources for treatment of Type 1 Diabetes Mellitus.

Dataset Information

Statistical approaches and software for clustering islet cell functional heterogeneity.

Publications

Statistical approaches and software for clustering islet cell functional heterogeneity.

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