Korean J Transplant.  2023 Nov;37(Suppl 1):S15. 10.4285/ATW2023.F-5799.

Modeling of allograft rejection using human induced pluripotent stem cell-derived kidney organoid system

• Lim SW
• Fang X
• Cui S
• Shin YJ
• Lee H
• Yang CW
• Chung BH

• KMID: 2551589
• DOI: http://doi.org/10.4285/ATW2023.F-5799

Abstract

Background
Kidney organoid derived human induced pluripotent stem cell (hiPSC) has been extensively studies as an alterna-tive cellular model for recapitulating phenotypic and pathophysiologic characters of human disease. In this study, we explored the potential of hiPSC-derived kidney organoid for rejection modeling.
Methods
Using WTC-11 hiPSC, we first evaluated whether IFNr treatment increase the human leukocyte antigen (HLA) expres-sion in the kidney organoids. Next, we determined if HLA-mismatched healthy volunteers peripheral blood mononuclear cell (PBMC) influence HLA expression by coculture system with kidney organoids. The expression changes of HLA (HLA-ABC and HLA-DR) was detected by analysis of confocal microscopy and flow cytometry. In addition, immunosuppressive effect by tacrolimus was also examined during HLA induction by IFNr or coculture system.
Results
Treatment of IFNr for 24 hours significantly increased the expression of HLA-ABC or HLA-DR with the nephron mark-ers (podocalyxin, lotus tetragonolobus lectin, e-cadherin) in the matured kidney organoids derived WTC-11 hiPSC by confirm-ing confocal microscopy and flow cytometric analysis. Next, after 24 hours coculture with HLA-mismatched PBMC and kidney organoids from WTC-11 hiPSC, we analyzed HLA expression after several wash out the PBMC from the kidney organoids. Consistently, the expression of HLA-ABC and HLA-DR was markedly increased compared with non-PBMC treatment and these induction was diminished by tacrolimus treatment dose-dependent manner.
Conclusions
These results showed the evidence that coculture system with allogeneic kidney organoid and PBMC can be potentially in vitro transplant rejection modeling. Therefore, this system has possibility of future application for finding a potential risk factors and studying drug screening of allograft rejection.