Generation of Human Renal Vesicles in Mouse Organ Niche Using Nephron Progenitor Cell Replacement System

Fujimoto, Toshinari; Yamanaka, Shuichiro; Tajiri, Susumu; Takamura, Tsuyoshi; Saito, Yatsumu; Matsumoto, Naoto; Matsumoto, Keīichi; Tachibana, Toshiaki; Okano, Hirotaka James; Yokoo, Takashi

doi:10.1016/j.celrep.2020.108130

Cited by 32 publications

(28 citation statements)

References 42 publications

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“…We have used metanephros as a scaffold to develop chimeric kidneys by subepithelial transplantation of allogeneic and heterologous nephron progenitors 16 - 18 . In the future, we will use the reaggregating spheroid transplantation method developed in this study to verify the appropriate cell ratio in chimeras and the factors that strongly generate interactions.…”

Section: Discussionmentioning

confidence: 99%

Techniques of fragile renal organoids transplantation in mice

et al. 2021

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Purpose: This study aimed to develop a microsurgical technique to transplant extremely fragile renal organoids in vivo , created by in-vitro reaggregation of metanephros from fetal mice. These organoids in reaggregation and development were examined histologically after transplantation under the renal capsule. Methods: Initially, metanephros from fetal mice were enzymatically treated to form single cells, and spheroids were generated in vitro . Under a microscope, the renal capsule was detached to avoid bleeding, and the outer cylinder of the indwelling needle was inserted to detach the renal parenchyma from the renal capsule using water pressure. The reaggregated spheroid was aspirated from the culture plate using a syringe with an indwelling needle outer cylinder and carefully extruded under the capsule. Pathological analysis was performed to evaluate changes in reaggregated spheroids over time and the effects of co-culture of spinal cord and subcapsular implantation on maturation. Results: In vitro , the formation of luminal structures became clearer on day 5. These fragile organoids were successfully implanted without tissue crapes under the renal capsule and formed glomerular. The effect of spinal cord co-transplant was not obvious histrionically. Conclusions: A simple and easy method to transplant fragile spheroids and renal under the renal capsule without damage was developed.

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Section: Discussionmentioning

confidence: 99%

Techniques of fragile renal organoids transplantation in mice

et al. 2021

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“…Regarding the regeneration of kidney organs that have a urinary tract, methods using the experimental animals’ body, such as interspecies blastocyst complementation [ 23 ] and organogenic niche method [ 24 ], have been investigated. Goto et al injected wild-type mESCs into the blastocysts of anephric Sall1(− / −) rats and succeeded in interspecifically generating mouse kidneys in the host rat [ 23 ].…”

Section: Kidney Developmentmentioning

confidence: 99%

“…Fujimoto et al developed a cell transplantation method through which hiPSC-derived NPCs were transplanted into the kidney development area (i.e. organogenic niche) of mouse embryos in uterine, in which the transplanted and host NPCs together contributed to the chimeric cap mesenchyme, which was connected to the host mouse UB [ 24 ]. However, while MM-derived glomeruli and renal tubule were derived from the injected PSCs or NPCs, the remaining kidney-constituent cell types, such as UB-derived collecting ducts and lower urinary tract and vascular cells, were from the host animals in these two strategies.…”

Section: Kidney Developmentmentioning

confidence: 99%

iPSC technology-based regenerative medicine for kidney diseases

Osafune

2021

Clin Exp Nephrol

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With few curative treatments for kidney diseases, increasing attention has been paid to regenerative medicine as a new therapeutic option. Recent progress in kidney regeneration using human-induced pluripotent stem cells (hiPSCs) is noteworthy. Based on the knowledge of kidney development, the directed differentiation of hiPSCs into two embryonic kidney progenitors, nephron progenitor cells (NPCs) and ureteric bud (UB), has been established, enabling the generation of nephron and collecting duct organoids. Furthermore, human kidney tissues can be generated from these hiPSC-derived progenitors, in which NPC-derived glomeruli and renal tubules and UB-derived collecting ducts are interconnected. The induced kidney tissues are further vascularized when transplanted into immunodeficient mice. In addition to the kidney reconstruction for use in transplantation, it has been demonstrated that cell therapy using hiPSC-derived NPCs ameliorates acute kidney injury (AKI) in mice. Disease modeling and drug discovery research using disease-specific hiPSCs has also been vigorously conducted for intractable kidney disorders, such as autosomal dominant polycystic kidney disease (ADPKD). In an attempt to address the complications associated with kidney diseases, hiPSC-derived erythropoietin (EPO)-producing cells were successfully generated to discover drugs and develop cell therapy for renal anemia. This review summarizes the current status and future perspectives of developmental biology of kidney and iPSC technology-based regenerative medicine for kidney diseases.

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“…Later, they developed a cell transplantation method through which hiPSC-derived NPCs were transplanted into the fetal kidney development area of embryonic day (E)13-14 mouse embryos in uterine. 22 The transplanted and host NPCs together contributed to the chimeric cap mesenchyme, which was connected to the host mouse UB. Like interspecies blastocyst complementation, however, this experimental approach generates chimeric kidneys in which MM-lineage cells are derived from donor PSCs, but other kidney constituents are from host animals.…”

Section: Reconstruction Of Kidney Tissues or Organsmentioning

confidence: 99%

“…The same study reported the generation of interspecific rat NPC‐derived nephrons. Later, they developed a cell transplantation method through which hiPSC‐derived NPCs were transplanted into the fetal kidney development area of embryonic day (E)13‐14 mouse embryos in uterine 22 . The transplanted and host NPCs together contributed to the chimeric cap mesenchyme, which was connected to the host mouse UB.…”

Section: Reconstruction Of Kidney Tissues or Organsmentioning

confidence: 99%

Regenerative treatments for kidney diseases: The closest and fastest strategies to solving related medical and economic problems

Osafune

2021

Artificial Organs

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Recent advances in developmental biology and stem cell biology have led to the increased availability of extrarenal stem cells, including mesenchymal/stromal stem cells (MSCs), renal stem or progenitor cells isolated from embryonic and adult kidneys, and kidney lineage cells or tissues generated from human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human-induced pluripotent stem cells. Regenerative medicine strategies for kidney diseases are largely categorized into the transplantation of reconstructed kidney organs and cell therapies.Reconstruction is being attempted by hPSC-derived kidney lineage cells with various strategies, such as self-organization, interspecies blastocyst complementation, utilization of a xenogeneic organ niche, decellularization and repopulation, and 3D bioprinting. However, cell therapies using extrarenal stem cells, such as MSCs, and renal stem or progenitor cells derived from embryonic and adult kidneys or differentiated from hPSCs have been investigated in animal models of both acute kidney injury and chronic kidney disease. Indeed, multiple clinical trials using MSCs, bone marrow stem cells, and kidney-derived cells have already been carried out. This review summarizes the current status and future perspective of kidney regenerative medicine strategies and discusses the closest and fastest strategies to solving the medical and economic problems associated with kidney diseases. K E Y W O R D Skidney disease, regenerative medicine, stem cell How to cite this article: Osafune K. Regenerative treatments for kidney diseases: The closest and fastest strategies to solving related medical and economic problems.

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Generation of Human Renal Vesicles in Mouse Organ Niche Using Nephron Progenitor Cell Replacement System

Cited by 32 publications

References 42 publications

Techniques of fragile renal organoids transplantation in mice

Techniques of fragile renal organoids transplantation in mice

iPSC technology-based regenerative medicine for kidney diseases

Regenerative treatments for kidney diseases: The closest and fastest strategies to solving related medical and economic problems

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