# Y-27632 dihydrochloride (BioGems 1293823)
J Transl Med. 2023 Feb 22;21(1):138. doi: 10.1186/s12967-023-03992-0
Sheng Cui 1, Xianying Fang 1, Hanbi Lee 1 2, Yoo Jin Shin 1, Eun-Sil Koh 3, Sungjin Chung 3, Hoon Suk Park 4, Sun Woo Lim 1, Kang In Lee 5, Jae Young Lee 5, Chul Woo Yang 1 2, Byung Ha Chung 6 7
- PMID: 36814269
- PMCID: PMC9948377
- DOI: 10.1186/s12967-023-03992-0
Abstract
Objectives: To explore the possibility of kidney organoids generated using patient derived human induced pluripotent stem cells (hiPSC) for modeling of Fabry disease nephropathy (FDN).
Methods: First, we generated hiPSC line using peripheral blood mononuclear cells (PBMCs) from two male FD-patients with different types of GLA mutation: a classic type mutation (CMC-Fb-001) and a non-classic type (CMC-Fb-003) mutation. Second, we generated kidney organoids using wild-type (WT) hiPSC (WTC-11) and mutant hiPSCs (CMC-Fb-001 and CMC-Fb-003). We then compared alpha-galactosidase A (α-GalA) activity, deposition of globotriaosylceremide (Gb-3), and zebra body formation under electromicroscopy (EM).
Results: Both FD patients derived hiPSCs had the same mutations as those detected in PBMCs of patients, showing typical pluripotency markers, normal karyotyping, and successful tri-lineage differentiation. Kidney organoids generated using WT-hiPSC and both FD patients derived hiPSCs expressed typical nephron markers without structural deformity. Activity of α-GalA was decreased and deposition of Gb-3 was increased in FD patients derived hiPSCs and kidney organoids in comparison with WT, with such changes being far more significant in CMC-Fb-001 than in CMC-Fb-003. In EM finding, multi-lammelated inclusion body was detected in both CMC-Fb-001 and CMC-Fb-003 kidney organoids, but not in WT.
Conclusions: Kidney organoids generated using hiPSCs from male FD patients might recapitulate the disease phenotype and represent the severity of FD according to the GLA mutation type.