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Updated: Jun 13, 2026
Murine Kidney Transplant Technique
Published on: October 20, 2015
Rat cell-derived kidney generation via interspecies blastocyst complementation in an Osr1-KO mouse model
Shunsuke Yuri1, Ayako Isotani2
1Laboratory of Experimental Animals, Research Institution, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi 474-8511, Japan; Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan.
Abstract:
Interspecies blastocyst complementation (BC) provides a promising approach to generate transplantable organs from pluripotent stem cells (PSCs). However, interspecies kidney generation has remained largely unsuccessful, particularly when using rat PSCs in mouse hosts. Here, we investigated multiple renal-deficient models (Sall1-, Ret-, and Osr1-knockouts [KOs]) through reverse BC (rBC) analyses. We identified Osr1-KO embryos as lacking both nephron progenitor and ureteric bud lineages, providing a vacant developmental niche for renal reconstruction. Injection of rat embryonic stem cells (ESCs) into Osr1-KO mouse blastocysts led to robust rat cell contribution and the formation of kidneys predominantly composed of rat in the vacant niche. These findings establish the Osr1-KO model as a permissive platform for interspecies kidney organogenesis and offer mechanistic insight into developmental compatibility underlying xenogeneic organ generation.
Insights
Generating rat kidneys in mice is now possible using a novel Osr1-knockout model. This breakthrough in interspecies kidney organogenesis utilizes reverse blastocyst complementation for xenogeneic organ generation.
Area of Science:
- Developmental Biology
- Regenerative Medicine
- Xenotransplantation
Background:
- Interspecies blastocyst complementation (BC) aims to generate organs from pluripotent stem cells (PSCs).
- Generating kidneys via BC, especially rat kidneys in mice, has been challenging.
- Previous models lacked suitable developmental niches for xenogeneic renal reconstruction.
Purpose of the Study:
- To identify a suitable mouse model for successful interspecies kidney organogenesis using rat PSCs.
- To investigate the potential of renal-deficient models for xenogeneic kidney generation.
- To understand the developmental compatibility factors in interspecies organogenesis.
Main Methods:
- Utilized reverse blastocyst complementation (rBC) analysis in mouse models.
- Investigated Sall1-, Ret-, and Osr1-knockout (KO) mouse embryos.
- Injected rat embryonic stem cells (ESCs) into Osr1-KO mouse blastocysts.
Main Results:
- Osr1-KO embryos were identified as lacking nephron progenitor and ureteric bud lineages, creating a vacant niche.
- Rat ESCs successfully contributed to kidney formation within the Osr1-KO mouse blastocyst niche.
- Generated kidneys were predominantly composed of rat cells, demonstrating successful xenogeneic organogenesis.
Conclusions:
- The Osr1-knockout mouse model provides a permissive platform for interspecies kidney organogenesis.
- This study offers mechanistic insights into developmental compatibility for xenogeneic organ generation.
- Successfully generated rat kidneys in mice, advancing the field of regenerative medicine.
