Abstract: PUB105
First-in-Class Phase 3 Clinical Trial Candidate Rilparencel Expresses Nephron Markers and Acquires Glomerular Epithelial and Tubular Features
Session Information
Category: Development, Stem Cells, and Regenerative Medicine
- 600 Development, Stem Cells, and Regenerative Medicine
Authors
- Narayan, Prakash, ProKidney, Winston-Salem, North Carolina, United States
- Bauer, Brooke, ProKidney, Winston-Salem, North Carolina, United States
- Trachtman, Howard, Renal Strategies LLC, New York, New York, United States
- Filler, Guido, Western University, London, Ontario, Canada
- Freedman, Benjamin S., University of Washington, Seattle, Washington, United States
- Stavas, Joseph, ProKidney, Winston-Salem, North Carolina, United States
- Butler, Emily Lynn, ProKidney, Winston-Salem, North Carolina, United States
- Bruce, Andrew T., ProKidney, Winston-Salem, North Carolina, United States
Background
Kidney cortical administration of rilparencel, a biopsy-derived autologous kidney epithelial cell platform, improves glomerular, tubular and urine concentrating profiles in chronic kidney disease (CKD) models & may support kidney function in type 2 diabetes (T2D)&CKD patients. We tested the hypothesis that rilparencel expresses markers spanning the nephron & acquires glomerular epithelial & tubular features.
Methods
Banked rilparencel samples from 5 T2D&CKD patients (NCT02836574) were analyzed with scRNAseq & kidney cell types & states identified with unsupervised clustering & projection on to the KPMP single cell CKD atlas. Organoids from rilparencel were grown for up to 17 d, sectioned & stained with periodic acid Schiff. Human rilparencel (discarded kidneys, NDRI) organoids in 3D culture were immunofluorescent antibody stained for nephron & glomerular epithelial precursors, HOXA11 & PTPRO (GUDMAP ATLAS-D2K), respectively, tubular epithelial markers, LTL & CD13 & the cycling cell marker, CDC6.
Results
KPMP-anchored molecularly profiled cell types constituting rilparencel include glomerular parietal epithelial cells (PECs), adaptive proximal tubules (PTs), ascending thin limb (ATL) & adaptive thick ascending limb-2 (TAL-2), distal convoluted tubule (DCT), connecting tubule (CNT) & intermediate collecting duct (IMCD). Proportions of each cell type were consistent amongst samples. Immunoflourescent antibody staining confirmed nephron & glomerular epithelial precursors, tubular epithelium & cycling cells. Sectioning of rilparencel organoids revealed morphologic features consistent with glomerular epithelium & tubules.
Conclusion
An integrated, cross-validating approach indicates that rilparencel expresses markers spanning the nephron & acquires glomerular epithelial & tubular features in culture. Increased nephron mass with both functional compartments may underlie beneficial effects of cortical delivery of rilparencel.
Funding
- Commercial Support – ProKidney