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Kidney Week

Abstract: PO0143

Although Human Mesenchymal Stem Cells Effectively Treat AKI in Rats, They Elicit an Immune Response, Abolishing Their Subsequent Protective Activity

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

Preclinical and clinical studies have shown renoprotective effects of allogeneic Mesenchymal Stem Cell Therapy (MSC) in preventing AKI, obtained without eliciting an antibody response, confirming MSCs' immune privileged/immune-modulating properties. Many groups have attempted to enhance MSCs’ potency by introducing beneficial genes via xenogeneic expression vectors. Whether such alterations conserve MSCs’ immune privileged characteristics is unknown. We here tested whether (1) the expression of human antigens by MSCs from Fischer344 (F344) rats transgenic for human Alkaline Phosphatase (hPAP-rMSC), human MSCs (hMSC) or human Adipose-derived Stem Cells (hASC) alters the cells’ renoprotective function in female F344 rats with IRI-induced AKI; (2) whether the administration of these cells elicits an antibody response; (3) whether such a response affects the reno-protective efficacy of the cells in subsequent treatments.

Methods

IRI AKI (42 min. bilateral pedicle clamp) was induced (n=6/group). Post reflow, groups were infused via the suprarenal aorta (s.a.) with hPAP-rMSC, hASCs or hMSC, 0.5-2x10e6 cells), or vehicle. Ten days post-AKI, serum samples were obtained and analyzed by FACS to assess for antigenic responses (IgG antibodies) to (1) MSC-specific genes, or (2) to hPAP. Two more groups of F344 rats (n=6 each) were inoculated i.p. with hASC (5x10e5). Immune response to hASCs was assessed 14 days post inoculation, and IRI AKI was induced as above, followed upon reflow by an identical s.a. infusion of hASCs or vehicle.

Results

Versus controls, all 3 cell types significantly protected renal function and hastened recovery from AKI (SCr levels, tissue injury scores); but within 14 days, each treatment elicited a significant IgG antibody response (57-99%) against the infused cell type. Rats inoculated i.p. with hASCs and confirmed to have positive immunity to hASCs were no longer renoprotected by hASCs when treated with them for IRI AKI.

Conclusion

While xenogeneic use of MSCs/ASCs is renoprotective, the demonstrated induction of an immune response makes such applications unsafe/ineffective in pre-clinical studies. Caution is advised in interpreting results of studies using cell lines containing xenogeneic expression vectors for genes meant to enhance MSCs’ clinical efficacy.
(Not U of Utah work)

Funding

  • Commercial Support