Porcine Kidney Organoids Derived from Naïve-like Embryonic Stem Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jan 11

PMID 38203853

Authors

Meishuang Li

Xiyun Guo

Linxin Cheng

Hong Zhang

Meng Zhou

Manling Zhang

Zhibao Yin

Tianxu Guo

Lihua Zhao

Han Liu

Xiubin Liang

Rongfeng Li

Affiliations

Soon will be listed here.

Abstract

The scarcity of donor kidneys greatly impacts the survival of patients with end-stage renal failure. Pigs are increasingly becoming potential organ donors but are limited by immunological rejection. Based on the human kidney organoid already established with the CHIR99021 and FGF9 induction strategy, we generated porcine kidney organoids from porcine naïve-like ESCs (nESCs). The derived porcine organoids had a tubule-like constructure and matrix components. The porcine organoids expressed renal markers including AQP1 (proximal tubule), WT1 and PODO (podocyte), and CD31 (vascular endothelial cells). These results imply that the organoids had developed the majority of the renal cell types and structures, including glomeruli and proximal tubules. The porcine organoids were also identified to have a dextran absorptive function. Importantly, porcine organoids have a certain abundance of vascular endothelial cells, which are the basis for investigating immune rejection. The derived porcine organoids might serve as materials for immunosuppressor screening for xenotransplantation.

Citing Articles

Generation of human-pig chimeric renal organoids using iPSC technology.

Fujimori K, Yamanaka S, Shimada K, Matsui K, Kawagoe S, Kuroda T Commun Biol. 2024; 7(1):1278.

PMID: 39375428 PMC: 11458617. DOI: 10.1038/s42003-024-06986-w.

Fetal Kidney Grafts and Organoids from Microminiature Pigs: Establishing a Protocol for Production and Long-Term Cryopreservation.

Inage Y, Fujimori K, Takasu M, Matsui K, Kinoshita Y, Morimoto K Int J Mol Sci. 2024; 25(9).

PMID: 38732014 PMC: 11084491. DOI: 10.3390/ijms25094793.

References

Morizane R, Lam A, Freedman B, Kishi S, Valerius M, Bonventre J . Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat Biotechnol. 2015; 33(11):1193-200. PMC: 4747858. DOI: 10.1038/nbt.3392. View

Loveland B, Milland J, Kyriakou P, Thorley B, Christiansen D, Lanteri M . Characterization of a CD46 transgenic pig and protection of transgenic kidneys against hyperacute rejection in non-immunosuppressed baboons. Xenotransplantation. 2004; 11(2):171-83. DOI: 10.1046/j.1399-3089.2003.00103.x. View

Gonzalez-Molina M, Ruiz-Esteban P, Caballero A, Burgos D, Cabello M, Leon M . Immune response and histology of humoral rejection in kidney transplantation. Nefrologia. 2016; 36(4):354-67. DOI: 10.1016/j.nefro.2016.03.023. View

van den Berg C, Ritsma L, Avramut M, Wiersma L, van den Berg B, Leuning D . Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo. Stem Cell Reports. 2018; 10(3):751-765. PMC: 5918682. DOI: 10.1016/j.stemcr.2018.01.041. View

Wijkstrom M, Iwase H, Paris W, Hara H, Ezzelarab M, Cooper D . Renal xenotransplantation: experimental progress and clinical prospects. Kidney Int. 2016; 91(4):790-796. PMC: 5357451. DOI: 10.1016/j.kint.2016.08.035. View

Namestnikov M, Pleniceanu O, Dekel B . Mixing Cells for Vascularized Kidney Regeneration. Cells. 2021; 10(5). PMC: 8148539. DOI: 10.3390/cells10051119. View

Yokoo T, Yamanaka S, Kobayashi E . Xeno-regenerative medicine: A novel concept for donor kidney fabrication. Xenotransplantation. 2020; 27(5):e12622. DOI: 10.1111/xen.12622. View

Park J, Ma W, OBrien L, Chung E, Guo J, Cheng J . Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks. Dev Cell. 2012; 23(3):637-51. PMC: 3892952. DOI: 10.1016/j.devcel.2012.07.008. View

Kumar S, Er P, Lawlor K, Motazedian A, Scurr M, Ghobrial I . Kidney micro-organoids in suspension culture as a scalable source of human pluripotent stem cell-derived kidney cells. Development. 2019; 146(5). PMC: 6432662. DOI: 10.1242/dev.172361. View

10.

Low J, Li P, Chew E, Zhou B, Suzuki K, Zhang T . Generation of Human PSC-Derived Kidney Organoids with Patterned Nephron Segments and a De Novo Vascular Network. Cell Stem Cell. 2019; 25(3):373-387.e9. PMC: 6731150. DOI: 10.1016/j.stem.2019.06.009. View

11.

Taguchi A, Kaku Y, Ohmori T, Sharmin S, Ogawa M, Sasaki H . Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. Cell Stem Cell. 2013; 14(1):53-67. DOI: 10.1016/j.stem.2013.11.010. View

12.

Takasato M, Little M . The origin of the mammalian kidney: implications for recreating the kidney in vitro. Development. 2015; 142(11):1937-47. DOI: 10.1242/dev.104802. View

13.

Cooper D . Genetically engineered pig kidney transplantation in a brain-dead human subject. Xenotransplantation. 2021; 28(6):e12718. PMC: 8717213. DOI: 10.1111/xen.12718. View

14.

Kang H, Lim J, Noh K, Park D, Cho H, Susztak K . Effective reconstruction of functional organotypic kidney spheroid for in vitro nephrotoxicity studies. Sci Rep. 2019; 9(1):17610. PMC: 6879515. DOI: 10.1038/s41598-019-53855-2. View

15.

Baumann B, Stussi G, Huggel K, Rieben R, Seebach J . Reactivity of human natural antibodies to endothelial cells from Galalpha(1,3)Gal-deficient pigs. Transplantation. 2007; 83(2):193-201. DOI: 10.1097/01.tp.0000250478.00567.e5. View

16.

Wu H, Uchimura K, Donnelly E, Kirita Y, Morris S, Humphreys B . Comparative Analysis and Refinement of Human PSC-Derived Kidney Organoid Differentiation with Single-Cell Transcriptomics. Cell Stem Cell. 2018; 23(6):869-881.e8. PMC: 6324730. DOI: 10.1016/j.stem.2018.10.010. View

17.

Takasato M, Er P, Chiu H, Maier B, Baillie G, Ferguson C . Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature. 2015; 526(7574):564-8. DOI: 10.1038/nature15695. View

18.

Mohiuddin M, Singh A, Scobie L, Goerlich C, Grazioli A, Saharia K . Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report. Lancet. 2023; 402(10399):397-410. PMC: 10552929. DOI: 10.1016/S0140-6736(23)00775-4. View

19.

Lu T, Yang B, Wang R, Qin C . Xenotransplantation: Current Status in Preclinical Research. Front Immunol. 2020; 10:3060. PMC: 6989439. DOI: 10.3389/fimmu.2019.03060. View

20.

Cooper D, Gaston R, Eckhoff D, Ladowski J, Yamamoto T, Wang L . Xenotransplantation-the current status and prospects. Br Med Bull. 2017; 125(1):5-14. PMC: 6487536. DOI: 10.1093/bmb/ldx043. View