Abstract: FR-PO701
Plasma From Patients With Focal Segmental Glomerulosclerosis Triggers an Abnormal Kidney Organoid Development With Specific Alteration in the Glomerular Structures and Podocytes
Session Information
- Glomerular Diseases: Podocyte Biology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1304 Glomerular Diseases: Podocyte Biology
Authors
- Gallon, Lorenzo G., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Gupta, Ashwani Kumar, The University of Arizona College of Medicine Phoenix, Phoenix, Arizona, United States
- Wertheim, Jason, The University of Arizona College of Medicine Phoenix, Phoenix, Arizona, United States
Background
Focal segmental glomerulosclerosis (FSGS) is a frequently acquired kidney disorder resulting in end-stage renal disease and it is associated with a high rate of recurrence after renal transplantation. Clinical and experimental evidence has shown that a circulating factor is involved in the pathogenesis of FSGS and its recurrence. We hypothesized that FSGS plasma could trigger an FSGS-specific abnormality in the glomerular structures and podocytes of kidney organoids.
Methods
The hPSCs were induced to differentiate in kidney organoids. On day 16, kidney organoid media was changed with fresh medium containing 10% healthy plasma, recurrent FSGS plasma, non-recurrent FSGS plasma, or primary FSGS plasma. On day 23, organoids were evaluated under a stereomicroscope, and organoids were stained for podocytes specific proteins, extracellular matrix (ECM) proteins, and injury molecules.
Results
Kidney organoids generated with organoid media and healthy plasma showed typical developmental phenotype with intact and tightly packed tubular clusters whereas organoids generated with FSGS plasma showed abnormal or damaged tubular clusters (Fig1. A-E). Podocalyxin staining for podocytes showed the organoids generated in organoid media and healthy plasma had intact presumptive glomerular structures (Fig1. F, G). Recurrent FSGS plasma-treated organoids and primary FSGS plasma-treated organoids showed damaged presumptive glomerular structures and scattered podocalyxin expression patterns (Fig1. I-J).
Gene expression analysis by qPCR of kidney organoids cultured with recurrent FSGS plasma or primary FSGS plasma vs media, healthy plasma, or non-recurrent FSGS plasma showed alteration of podocytes specific proteins.
Conclusion
FSGS plasma can trigger FSGS specific abnormality in the glomerular structures and podocytes. FSGS plasma induce podocyte and proximal tubule injury. Our kidney organoid model could be a useful tool to study the pathophysiology of primary FSGS.
Phenotypic changes to kidney organoids after FSGS plasma treatment.
Funding
- Other U.S. Government Support