Evaluation of the ability of human induced nephron progenitor cells to form chimeric renal organoids using mouse embryonic renal progenitor cells

Matsumoto, Naoto; Yamanaka, Shuichiro; Morimoto, Keita; Matsui, Kenji; Nishimura, Sandy; Kinoshita, Yoshitaka; Inage, Yuka; Fujimori, Koki; Kuroda, Takao; Saito, Yatsumu; Takamura, Tsuyoshi; Fujimoto, Toshinari; Tajiri, Susumu; Matsumoto, Keīichi; Kobayashi, Eiji; Yokoo, Takashi

doi:10.1016/j.bbrc.2023.04.052

Cited by 2 publications

(7 citation statements)

References 25 publications

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“…The conditions utilizing NPC_Re-agg as the reaggregation medium and NPC_Mat as the maturation medium improved the formation of human, mouse, and human-mouse chimeric organoids, compared to the previous report[20]. Additionally, the composition of the medium was shown to influence the ratio of components in the chimera.…”

Section: Resultsmentioning

confidence: 78%

“…The production of fetal mouse kidney organoids, in which fetal kidneys are enzymatically processed, aggregated from a single-cell state, and subsequently reconstructed to recapitulate renal structures, has been documented in previous studies[24,25]. Leveraging the self-organization of fetal kidney progenitor cells, we demonstrated the incorporation of human iPSC-derived NPCs during fetal kidney organoid formation, resulting in the formation of interspecies human-mouse chimeric nephrons[20]. However, while we initially considered the survival and organoid formation of cell types constituting the kidney organoids to be crucial, it became evident in our approach that the survival and organoid formation of human NPCs were not sufficient (SupFig.…”

Section: Resultsmentioning

confidence: 80%

“…Single cells from mouse and pig fetal kidneys were obtained following a previously reported method [20,25,44]. Fetal kidneys were harvested from the decapitated fetuses under an operating microscope and collected in 1.5 mL tubes containing a minimum essential medium (MEMa; Thermo Fisher Scientific, Inc.).…”

Section: Single Cell Extraction From Fetal Kidneysmentioning

confidence: 99%

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Generation of human-pig chimeric renal organoids using iPSC technology

Fujimori,

Yamanaka,

Shimada

et al. 2024

Preprint

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The potential of using porcine organs and human induced pluripotent stem cell (iPSC)-derived organoids as alternative organs for human transplantation has garnered growing attention. However, both approaches still face technological challenges. Interspecies chimeric organ production using human iPSCs is expected to be another promising approach that addresses the challenges associated with organ production. Our research group successfully generated human-mouse chimeric renal organoids by utilizing human iPSC-derived nephron progenitor cells (NPCs) and fetal mouse kidneys. However, the current technology has limited engraftment and development capabilities for human NPCs, and there have been no reports of generating interspecies chimeric renal organoids in larger animals, limited only to rodents. Therefore, in this study, we embarked on the production of human-pig chimeric renal organoids using the pig kidney, which is considered the most promising source of organs for interspecies transplantation to humans. To construct a human-pig chimeric renal organoid culture system, we first modified the existing human-mouse chimeric renal organoid culture system and developed a method that enables the survival and continued renal development of both species. This method was found to be applicable to porcine fetal kidney cells, and ultimately, we successfully produced human-pig chimeric renal organoids. Furthermore, this culture method can also be applied to the generation of human interspecies chimeric kidneys for future clinical applications. The findings of this study serve as a foundational technology that will greatly accelerate future research in humanized pig kidney production for clinical purposes, and are also expected to be used as an evaluation technique to ensure the quality of human NPCs for xenotransplantation.

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Section: Resultsmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 80%

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Generation of human-pig chimeric renal organoids using iPSC technology

Fujimori,

Yamanaka,

Shimada

et al. 2024

Preprint

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“…The culture condition for mouse fetal kidney spheroids were not appropriated for pig spheroids [11]. Therefore, leveraging insights showing that spheroid maturation can be facilitated in vivo [19,20], we chose to validate the viability of spheroids in vivo.…”

Section: In Vivo Differentiation Capacity Of Cells Harvested From Vit...mentioning

confidence: 99%

“…It is known that the same cell types from different species form chimeric homogeneous cell clusters [10]. Recently, human and mouse chimeric renal organoids were generated by co-culturing mouse fetal kidney cells with induced human NPCs [11]. While chimeric organoids comprising human and pig progenitor cells have not been reported to date, they could serve as valuable tools for studying the differences in developmental processes and inter-species barriers between humans and pigs to generate mature chimeric organs.…”

Section: Introductionmentioning

confidence: 99%

Exploration of Preservation Methods for Utilizing Porcine Fetal-Organ-Derived Cells in Regenerative Medicine Research

Matsui,

Sekine,

Ishikawa

et al. 2024

Cells

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Human pluripotent stem cells have been employed in generating organoids, yet their immaturity compared to fetal organs and the limited induction of all constituent cell types remain challenges. Porcine fetal progenitor cells have emerged as promising candidates for co-culturing with human progenitor cells in regeneration and xenotransplantation research. This study focused on identifying proper preservation methods for porcine fetal kidneys, hearts, and livers, aiming to optimize their potential as cell sources. Extracted from fetal microminiature pigs, these organs were dissociated before and after cryopreservation–thawing, with subsequent cell quality evaluations. Kidney cells, dissociated and aggregated after vitrification in a whole-organ form, were successfully differentiated into glomeruli and tubules in vivo. In contrast, freezing hearts and livers before dissociation yielded suboptimal results. Heart cells, frozen after dissociation, exhibited pulsating heart muscle cells similar to non-frozen hearts. As for liver cells, we developed a direct tissue perfusion technique and successfully obtained highly viable liver parenchymal cells. Freezing dissociated liver cells, although inferior to their non-frozen counterparts, maintained the ability for colony formation. The findings of this study provide valuable insights into suitable preservation methods for porcine fetal cells from kidneys, hearts, and livers, contributing to the advancement of regeneration and xenotransplantation research.

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Evaluation of the ability of human induced nephron progenitor cells to form chimeric renal organoids using mouse embryonic renal progenitor cells

Cited by 2 publications

References 25 publications

Generation of human-pig chimeric renal organoids using iPSC technology

Generation of human-pig chimeric renal organoids using iPSC technology

Exploration of Preservation Methods for Utilizing Porcine Fetal-Organ-Derived Cells in Regenerative Medicine Research

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