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Abstract: PO0935

Durable Euglycemia by Intraperitoneal Administration of Allogeneic Neo-Islets, 3D Organoids of Pancreatic Islet and Mesenchymal Stem Cells, Effectively Reduces Diabetic Nephropathy in Immune-Component Non-Obese Diabetic Mice

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Westenfelder, Christof, SymbioCellTech, LLC, Salt Lake City, Utah, United States
  • Gooch, Anna, SymbioCellTech, LLC, Salt Lake City, Utah, United States
  • Chowdhury, Sabiha Sultana, SymbioCellTech, LLC, Salt Lake City, Utah, United States
  • Zhang, Ping, SymbioCellTech, LLC, Salt Lake City, Utah, United States
  • Hu, Zhuma, SymbioCellTech, LLC, Salt Lake City, Utah, United States
Background

We demonstrated that the i.p. administration of allogeneic “Neo-Islets” (NIs), 3-D organoids of culture expanded Pancreatic Islet (PI) and Mesenchymal Stem Cells (MSC), induces permanent euglycemia without the need for anti-rejection drugs in NOD mice with auto-immune Type I Diabetes mellitus (T1DM). The NIs engraft in the omentum and physiologically deliver insulin and other islet hormones into the hepatic portal system, while providing auto- and allo-immune isolation, up regulate T-regs, stimulate angiogenesis, prevent apoptosis and inflammation. As a significant percentage of patients with T1DM develop diabetic nephropathy (DNP) and other end organ damage, we tested whether the induction of stable euglycemia in NOD mice would prevent or ameliorate DNP.

Methods

Three Groups of adult mice (n=7 each; ~25 g b.wt.; age 12 weeks) were examined: (1) Non-diabetic, age and sex matched C57/Bl6 mice; (2) Vehicle treated NOD mice with fully developed auto-immune T1DM; (3) NI treated NOD mice with normal blood glucose levels. Animals were followed for 21 weeks post treatment (blood glucose levels, body weights, blood pressures, proteinuria, renal function).

Results

At the termination of the study, kidneys from all groups were examined for glomerulosclerosis and interstitial fibrosis (Trichrome staining). The vehicle treated NOD mice (Group 2) had blood glucose levels of 400-600 mg/dL, lost weight, had systolic hypertension and showed extensive interstitial fibrosis, glomerulosclerosis, proteinuria, hypertension and elevated SCr and BUN levels, while NI treated, euglycemic NOD mice (Group 3) showed significantly lower degrees of glomerulosclerosis, interstitial fibrosis, proteinuria, hypertension and better preserved renal function. All tested variables remained normal in non-diabetic Group 1 control mice.

Conclusion

The presented data demonstrate that NI therapy-induced normalization of glycemia significantly improves the manifestations of DNP without fully correcting them when compared to non-diabetic controls. Modifications in NI treatment protocols are expected to further improve the development of DNP, which, if successful, would further strengthen the translational relevance of this novel therapy.
(No U of Utah resources used.)

Funding

  • Commercial Support