Abstract: PO0144
Point-of-Care Prevention and Treatment of AKI with Adipose-Derived Stem Cells: Efficacy and Cost Advance over Culture-Expanded Bone Marrow-Derived Mesenchymal Stem Cells
Session Information
- AKI Mechanisms - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 101 AKI: Epidemiology, Risk Factors, and Prevention
Authors
- Gooch, Anna, 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
- Westenfelder, Christof, SymbioCellTech, LLC, Salt Lake City, Utah, United States
Background
Our pre-clinical studies (AJP 2005) and a Phase I Clinical Trial (Nat Rev Neph 2010) show that administration of bone marrow-derived, culture expanded, allogeneic Marrow Stromal Cells (MSC) is effective in the prevention and hastened recovery from experimental AKI; and safe and renoprotective in on-pump cardiac surgery patients at high risk for post-op AKI. Significantly, MSC treated unlike historical control on-pump cardiac surgery patients did not develop Chronic Kidney Disease (CKD) long term (>7 years). Expansion and banking of MSCs is expensive and time consuming. To address these limitations, we compared treatment with syngeneic, culture-expanded MSCs or vehicle to treatment with either syngeneic, minimally manipulated abdominal Adipose Derived Stem Cells (ASCs) or autologous Stromal Vascular Fraction (SVF, immediately isolated from fat, containing ASCs, endothelial precursor and other cells) for efficacy in preventing AKI. ASCs share therapeutically critical activities with MSCs and are found in sufficiently high numbers/gram fat to present an alternative to culture-expanded MSCs.
Methods
ASCs and SVFs were isolated by minimal processing from abdominal fat harvested from male Fisher344 (F344) rats. IRI AKI was induced (bilateral renal pedicle clamping x 40 min) in 5 groups of male F344 rats (~200 g b.wt.; n=7 each). Upon reflow, groups were infused (suprarenal aorta) with either (1) 1x106 ASCs, (2) 1x106 autologous SVF cells, (3) 1x106 syngeneic, cultured MSCs, (4 and 5) vehicle in animals with or without fat harvest.
Results
Outcomes were compared to those of sham treated animals (n=7). Renal function assessed by serum Cr (SCr) in ASC or SVF treated animals was significantly better protected, and recovery more rapidly achieved compared to vehicle and MSC treated rats.
Conclusion
Our data suggest therefore that autologous ASCs and the SVF, obtained by minimal manipulation from a patient’s lipoaspirate, have the potential to treat that same patient with an efficient, inexpensive and safe point-of-care protocol to prevent or treat AKI and prevent subsequent progression to CKD.
(No University of Utah resources were used for this work.)
Funding
- Commercial Support –