| 초록 |
Objectives: Chronic kidney disease (CKD) has emerged as a crucial healthcare issue worldwide. Regenerative medicine, in which the nephrons lost during the progression of CKD are replaced by stem cells, is potential attractive therapeutic option for CKD. Recently, we and others established protocols for the generation of kidney organoids from human pluripotent stem cells (hPSCs). However, organoids generated in vitro are immature, and it remains unclear whether kidney organoids transplanted into kidneys in vivo, can replace the nephrons lost during kidney injury. Here, we transplanted kidney organoids derived from induced pluripotent stem cells (iPSCs) into the kidneys of NOD-SCID mice.
Methods: The CMC11 iPSC cell line was obtained from The Catholic University of Korea (male donor). Kidney organoid differentiation from the CMC11 iPSCs was performed using an adherent protocol. Kidney organoids were transplanted subcapsularly into the kidney of NOD-SCID mice. Transplanted mice were sacrificed at 7 days, 10 days, 14 days, 28 days, and 42 days after transplantation
Results: We demonstrate that kidney organoids have extended survival after transplantation, with vascularization by endothelial cells from the host mouse kidney. Furthermore, transplantation of kidney organoids into mouse kidneys enhanced nephron maturation compared with kidney organoids in vitro. Structures resembling glomeruli, Bowman’s capsules, the filtration barrier-like structures and tubules were observed. Ultrastructure of the filtration barrier-like structures and tubules of the transplanted kidney organoids resembles that of the adult mouse kidney. Kidney organoids also survived when they were transplanted into mouse kidneys with unilateral ureteral obstruction, an experimental model of progressive tubulointerstitial fibrosis.
Conclusions: These results suggest that the transplantation of kidney organoids derived from iPSCs may be a therapeutic option in CKD.
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