ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2021 and some content may be unavailable. To unlock all content for 2021, please visit the archives.

Abstract: PO0644

Treatment of Diabetic NOD/SCID Mice with Human "Neo-Islets," 3D Organoids of Mesenchymal Stromal and Pancreatic Islet Cells, Normalizes Blood Glucose Levels: Significance for Clinical Trials

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Westenfelder, Christof, University of Utah Hospital, Salt Lake City, Utah, United States
  • Gooch, Anna, SymbioCellTech, Salt Lake City, Utah, United States
Background

We reported that allogeneic “Neo-Islets” (NI) are immune protected and permanently correct autoimmune diabetes in NOD mice by omental engraftment and endocrine cell redifferentiation. This new “endocrine pancreas” delivers islet hormones physiologically into the hepatic portal vein. Further, treatment of insulin-dependent dogs with allogeneic canine NIs (ongoing FDA-approved Pilot Study) consistently improved glycemic control without the need for antirejection drugs. The current preclinical study was undertaken in anticipation of a Phase 1 Clinical Trial with two objectives: to determine (a) whether human NIs (hNIs) can also restore euglycemia, and (b) whether redosing of suboptimally controlled diabetic animals could restore euglycemia in streptozotocin (STZ)-diabetic NOD/SCID mice, as has been previously shown for mouse and dog cell-derived NIs.

Methods

Passaged cells that were to be used to treat diabetic NOD/SCID mice were characterized for gene expression profiles by rtPCR. For in vivo testing, NOD/SCID mice were made diabetic with STZ, then randomized based on blood glucose levels into groups of 6 each, treated with insulin pellets, and once blood glucose levels were stabilized near normal animals were treated i.p. either with ~2x10e5 human cell-derived NIs/kg bw (n=6) or vehicle (n=6), then followed for 8 weeks. Once blood glucose levels were determined to be no longer significantly improved compared to controls without administration of exogenous insulin, mice in each group were again treated with either 2x10e5 NIs/kg bw or vehicle, and followed for an additional 6 weeks. Therapeutic efficacy was assessed by survival, 2x weekly blood glucose monitoring, and glucose tolerance tests administered 57 and 41 days post the 1st and 2nd doses, respectively.

Results

Human NI therapy significantly improved glycemic control and survival vs. vehicle. A 2nd dose given to the initial group normalized blood glucose levels long-term.

Conclusion

Despite the limitations of the diabetic NOD/SCID model, these data show that human NIs are curative, and in conjunction with data from the dog study, where allogeneic NI therapy reduces the need for insulin without need for antirejection drugs, have high translational relevance and support the planned conduct of human NI clinical trials.

Funding

  • Commercial Support –