Abstract: FR-PO265
Prevention of Diabetic Nephropathy with Mesenchymal Stromal Cells in Cardiac Surgery Patients and in Nonobese Diabetic (NOD) Mice and Diabetic Dogs with "Neo-Islets," Three-Dimensional Organoids of Mesenchymal Stem Cells (MSCs), and Pancreatic Islet Cells
Session Information
- Diabetic Kidney Disease: Basic - 1
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Westenfelder, Christof, University of Utah Health, Salt Lake City, Utah, United States
- Gooch, Anna, SymbioCellTech, LLC, Salt Lake City, Utah, United States
Background
The most common cause of dialysis requiring ESKD is DNP.
Prevention of this serious complication is urgently needed. We addressed this need by utilizing the potent capacity of MSCs to prevent AKI and 2° CKD and to provide immune isolation in Neo-Islet (NI) treated autoimmune T1DM. In a Clinical Trial (NCT00733876) in cardiac surgery patients, at high risk for post-op AKI, we compared the renoprotective efficacy of allogeneic MSCs in diabetic to that in non-diabetic subjects. In 2 preclinical studies we investigated whether the therapy of auto-immune T1DM in NOD mice and dogs (INAD012-776) with allogeneic NIs would prevent DNP.
Methods
Clinical Trial: 16 adult patients, 7 diabetic, undergoing on-pump cardiac surgery (CABG ± valve) and being at high risk for post-op AKI were infused via the suprarenal aorta with allogeneic MSCs. Vital signs, renal function and glycemic control were monitored for 10 yrs and compared to those of well-matched historical controls (n=105). Therapy (i.p.) of diabetic NOD mice and dogs with allogeneic NIs: the response of diabetic NOD mice (n=7) vs. controls (n=7) was monitored x 12 wks and in diabetic dogs (n=9) x 3 yrs. Immune responses and mouse renal pathologies were examined.
Results
Clinical Trial: none of the MSC treated diabetic and non-diabetic patients developed post-op AKI or progressed over 10 years to DNP/ESKD. No mortality and no allo-immune response. In contrast, a significant percentage of historical controls developed post-op AKI, progressed to ESKD and suffered mortalitiy. Response of diabetic NOD mice and dogs to NIs: All NOD mice became euglycemic, none developed DNP, while diabetic controls did. Daily insulin needs of TIDM dogs were durably (3 yrs) reduced by 50% (p< 0.01), body weights were stable, blood glucose and HbA1C levels and albuminuria were normalized, renal and liver functions, lipid profiles and CBCs remained normal, and no immune responses to NIs or AEs/SAEs were observed.
Conclusion
These studies demonstrate that these biotherapies prevented the development of DNP and ESKD, and this without the need for anti-rejection drugs. The FDA approved the conduct of our IND-enabling study needed for the planned Phase I/II Clinical Trial in which the therapeutic efficacy of human NIs will be tested in T1DM subjects.
Funding
- Commercial Support – SymbioCellTech