News & Events

Grants, last few years

NIH/NIDDK Phase II SBIR awarded Sept 2015

Human induced pluripotent stem cell-derived beta-cells for drug and toxicity testing.

NIH/NIDDK Phase 1 SBIR awarded July 2016

Diabetes drug screening platforms using patient pancreatic islet-like cells generated from induced pluripotent stem cells.

NIH/NIDDK Phase I SBIR awarded Sept 2016

Development of a rapid and inexpensive luciferase-based high throughput screening assay to identify compounds that alter pancreatic β cell function.

NIH/NIDDK Phase I SBIR awarded Sept 2016

Engineered pancreatic endocrine cells that report beta cell toxicity for use in high throughput screening applications.

WI SBIR Advance awarded 2017

WI SBIR Advance awarded 2017

NIH GRANTS 2022

                        Development of a safer stem cell-based diabetes therapy via suicide gene-mediated ablation of proliferative cells.

                                  Evaluation of a beta cell replacement therapy combined product that avoids the need for immunosuppression via localized induction of immune tolerance

Intracameral Microimaging of Maturation of Human iPSC Derivatives into Islet Endocrine Cells

Abstract

We exploited the anterior chamber of the eye (ACE) of immunodeficient mice as an ectopic site for both transplantation and microimaging of engineered surrogate islets from human induced pluripotent stem cells (hiPSC-SIs). These islets contained a majority of insulin-expressing cells, positive or negative for PDX1 and NKX6.1, and a minority of glucagon- or somatostatin-positive cells. Single, non-aggregated hiPSC-SIs were satisfactorily engrafted onto the iris. They underwent gradual vascularization and progressively increased their light scattering signals, reflecting the abundance of zinc-insulin crystal packaged inside mature insulin secretory granules. Intracameral hiPSC-SIs retrieved from recipients showed enhanced insulin immunofluorescence in correlation with the parallel increase in overall vascularization and light backscattering during the post-transplantation period. This approach enables longitudinal, nondestructive and intravital microimaging of cell fates, engraftment, vascularization and mature insulin secretory granules of single hiPSC-SI grafts, and may offer a feasible and reliable means to screen compounds for promoting in vivo hiPSC-SI maturation.

Keywords: backscattering; human induced pluripotent stem cells (hiPSCs); in vivo confocal microscopy; surrogate islet; the anterior chamber of the eye (ACE); transplantation; vascularization.

Conflict of interest statement

Declaration of Conflicting Interests: P-OB is the founder and CEO of the biotech company BioCrine AB. S-NY is a consultant to BioCrine. AK and JO are co-founders of Regenerative Medical Solutions, Inc. and have equity interest in the company. The research reported here was supported in part by funding provided by Regenerative Medical Solutions, Inc. AM, and TJ are employees of Regenerative Medical Solutions, Inc.

 

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