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Abstract: SA-PO127

Intraperitoneal Administration of Human “Neo-Islets” Composed of Equal Numbers of Mesenchymal Stem and Pancreatic Islet Cells Durably Corrects Hyperglycemia in Diabetic NOD/SCID Mice

Session Information

Category: Diabetes

  • 503 Diabetes Mellitus and Obesity: Translational

Authors

  • Westenfelder, Christof, University of Utah and VA Medical Centers, Salt Lake City, Utah, United States
  • Gooch, Anna, University of Utah and VA Medical Centers, Salt Lake City, Utah, United States
  • Hu, Zhuma, University of Utah and VA Medical Centers, Salt Lake City, Utah, United States
  • Zhang, Ping, University of Utah and VA Medical Centers, Salt Lake City, Utah, United States
Background

Globally, individuals with autoimmune Type 1 Diabetes mellitus (T1DM) continue to depend for survival on insulin injections. While pancreas and intrahepatic pancreatic islet transplants can produce insulin-independence and ameliorate serious complications, both therapies depend on potentially toxic anti-rejection drugs. Furthermore, the scarcity of pancreas donors, islet transplant failures, and the inability to adequately culture expand insulin-producing β-cells significantly limit the general availability of such and other cell-based interventions. Encapsulation of islets to protect them from allo- and auto-immune destruction has shown both promise and failures. We reported recently [STEM CELLS Translational Medicine, 7, 2017] that allogeneic “Neo-Islets” (NI) are immune protected and correct autoimmune diabetes in NOD mice. Furthermore, we are conducting an FDA-approved Pilot Study with canine NIs in insulin-dependent dogs using identical technology. As there remains a critical need for curative therapies of T1DM, we engineered human NIs and tested their ability, after i.p. administration, to reestablish euglycemia in streptozotocin (STZ)-diabetic NOD/SCID mice.

Methods

We generated ex vivo islet-sized NIs in which culture-expanded islet cells were aggregated in cell clusters with equal numbers of MSCs. NIs (5x10e6/kg b.wt.) or vehicle were administered i.p. to groups (n=6 each) of STZ-diabetic NOD/SCID mice.

Results

This minimally invasive i.p. administration of NIs durably normalized blood glucose levels in diabetic NOD/SCID mice. This was achieved by the spontaneous engraftment of NIs in the animals’ omenta, and spontaneous redifferentiation of NI-intrinsic islet cells that physiologically secrete insulin into the hepatic portal vein.

Conclusion

Human NIs, as engineered here, show promise as a novel therapy that, we posit, has significant translational relevance to clinical T1DM. Specifically, this technology addresses the need for anti-rejection drugs and overcomes the scarcity of suitable donors.

Funding

  • Commercial Support