Concerns over the Safety and Maturity of Nephron-Like Structures after Renal Subscapular Transplantation of Kidney Organoids Derived from Human iPS Cells
- Transplantation: Back to the Basics
October 27, 2018 | Location: 6D, San Diego Convention Center
Abstract Time: 04:42 PM - 04:54 PM
- 1801 Transplantation: Basic
- Kim, Yong Kyun, Catholic University of Korea, Seoul, Korea (the Republic of)
- Freedman, Benjamin S., University of Washington, Seattle, Washington, United States
For chronic kidney disease, regeneration of lost nephrons in human kidney organoids derived from induced pluripotent stem (iPS) cells is proposed to be an attractive potential therapeutic option, but it remains unclear whether kidney organoids transplanted into kidneys in vivo would be safe or functional.
Kidney organoids were differentiated from the CMC11 iPS cell line using the protocols decribed previously. The harvested kidney organoids were transplanted into subcapsular space of kidneys of immunodeficient male NOD/SCID mice.
Kidney organoid grafts survived for months after transplantation and were vascularized from host mouse endothelial cells. Transplantation of kidney organoids into mouse kidneys revealed nephron-like structures with more mature characteristics, compared with kidney organoids in vitro, but they remained immature. Ultrastructural analysis revealed the filtration barrier-like structures, capillary lumens and tubules with brush border in the transplanted kidney organoids, which were more mature than those of the kidney organoids in vitro but not organized as adult mammalian kidneys. Stroma of transplanted kidney organoid grafts were filled with vimentin-positive mesenchymal cells, and cells in nephron-like structures were similarly not fully differentiated. Chondrogenesis and cystogenesis were observed in the transplanted kidney organoid grafts in the long term, characteristics reminiscent of teratoma tumors.
Our data suggest that kidney organoids derived from iPS cells may be transplantable but strategies for overcoming the immaturity and maldifferentiation are needed before they can be used in humans as a therapeutic option for nephron loss.