Enhancing Maturity in 3D Kidney Micro-tissues Through Clonogenic Cell Combinations and Endothelial Integration

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2024 May 31

PMID 38818569

Authors

Fatemeh Abdollahzadeh

Niloofar Khoshdel-Rad

Khadijeh Bahrehbar

Saiedeh Erfanian

Vahid Ezzatizadeh

Mehdi Totonchi

Reza Moghadasali

Affiliations

Soon will be listed here.

Abstract

As an advance laboratory model, three-dimensional (3D) organoid culture has recently been recruited to study development, physiology and abnormality of kidney tissue. Micro-tissues derived from primary renal cells are composed of 3D epithelial structures representing the main characteristics of original tissue. In this research, we presented a simple method to isolate mouse renal clonogenic mesenchymal (MLCs) and epithelial-like cells (ELCs). Then we have done a full characterization of MLCs using flow cytometry for surface markers which showed that more than 93% of cells expressed these markers (Cd44, Cd73 and Cd105). Epithelial and stem/progenitor cell markers characterization also performed for ELC cells and upregulating of these markers observed while mesenchymal markers expression levels were not significantly increased in ELCs. Each of these cells were cultured either alone (ME) or in combination with human umbilical vein endothelial cells (HUVECs) (MEH; with an approximate ratio of 10:5:2) to generate more mature kidney structures. Analysis of 3D MEH renal micro-tissues (MEHRMs) indicated a significant increase in renal-specific gene expression including Aqp1 (proximal tubule), Cdh1 (distal tubule), Umod (loop of Henle), Wt1, Podxl and Nphs1 (podocyte markers), compared to those groups without endothelial cells, suggesting greater maturity of the former tissue. Furthermore, ex ovo transplantation showed greater maturation in the constructed 3D kidney.

Citing Articles

Enhancing maturity in 3D kidney micro-tissues through clonogenic cell combinations and endothelial integration.

Abdollahzadeh F, Khoshdel-Rad N, Bahrehbar K, Erfanian S, Ezzatizadeh V, Totonchi M J Cell Mol Med. 2024; 28(11):e18453.

PMID: 38818569 PMC: 11140233. DOI: 10.1111/jcmm.18453.

References

Zahmatkesh E, Khoshdel-Rad N, Mirzaei H, Shpichka A, Timashev P, Mahmoudi T . Evolution of organoid technology: Lessons learnt in Co-Culture systems from developmental biology. Dev Biol. 2021; 475:37-53. DOI: 10.1016/j.ydbio.2021.03.001. View

Dhimolea E, Maffini M, Soto A, Sonnenschein C . The role of collagen reorganization on mammary epithelial morphogenesis in a 3D culture model. Biomaterials. 2010; 31(13):3622-30. DOI: 10.1016/j.biomaterials.2010.01.077. View

Takebe T, Enomura M, Yoshizawa E, Kimura M, Koike H, Ueno Y . Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation. Cell Stem Cell. 2015; 16(5):556-65. DOI: 10.1016/j.stem.2015.03.004. View

Abdollahzadeh F, Khoshdel-Rad N, Moghadasali R . Kidney development and function: ECM cannot be ignored. Differentiation. 2022; 124:28-42. DOI: 10.1016/j.diff.2022.02.001. View

Khoshdel-Rad N, Ahmadi A, Moghadasali R . Kidney organoids: current knowledge and future directions. Cell Tissue Res. 2022; 387(2):207-224. PMC: 8794626. DOI: 10.1007/s00441-021-03565-x. View

Garreta E, Prado P, Tarantino C, Oria R, Fanlo L, Marti E . Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells. Nat Mater. 2019; 18(4):397-405. PMC: 9845070. DOI: 10.1038/s41563-019-0287-6. View

Santoro D, Caccamo D, Lucisano S, Buemi M, Sebekova K, Teta D . Interplay of vitamin D, erythropoiesis, and the renin-angiotensin system. Biomed Res Int. 2015; 2015:145828. PMC: 4427087. DOI: 10.1155/2015/145828. View

Inoue C, Kondo Y, Ohnuma S, Morimoto T, Nishio T, Iinuma K . Use of cultured tubular cells isolated from human urine for investigation of renal transporter. Clin Nephrol. 2000; 53(2):90-8. View

Mugford J, Sipila P, McMahon J, McMahon A . Osr1 expression demarcates a multi-potent population of intermediate mesoderm that undergoes progressive restriction to an Osr1-dependent nephron progenitor compartment within the mammalian kidney. Dev Biol. 2008; 324(1):88-98. PMC: 2642884. DOI: 10.1016/j.ydbio.2008.09.010. View

10.

Saran R, Robinson B, Abbott K, Agodoa L, Bragg-Gresham J, Balkrishnan R . US Renal Data System 2018 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2019; 73(3 Suppl 1):A7-A8. PMC: 6620109. DOI: 10.1053/j.ajkd.2019.01.001. View

11.

Rubera I, Tauc M, Bidet M, Poujeol C, Cuiller B, Watrin A . Chloride currents in primary cultures of rabbit proximal and distal convoluted tubules. Am J Physiol. 1998; 275(5):F651-63. DOI: 10.1152/ajprenal.1998.275.5.F651. View

12.

Khoshdel-Rad N, Zahmatkesh E, Moeinvaziri F, Haghparast N, Baharvand H, Aghdami N . Promoting Maturation of Human Pluripotent Stem Cell-Derived Renal Microtissue by Incorporation of Endothelial and Mesenchymal Cells. Stem Cells Dev. 2021; 30(8):428-440. DOI: 10.1089/scd.2020.0189. View

13.

Yengej F, Jansen J, Rookmaaker M, Verhaar M, Clevers H . Kidney Organoids and Tubuloids. Cells. 2020; 9(6). PMC: 7349753. DOI: 10.3390/cells9061326. View

14.

Kamiyama M, Garner M, Farragut K, Kobori H . The establishment of a primary culture system of proximal tubule segments using specific markers from normal mouse kidneys. Int J Mol Sci. 2012; 13(4):5098-5111. PMC: 3344268. DOI: 10.3390/ijms13045098. View

15.

Takebe T, Sekine K, Kimura M, Yoshizawa E, Ayano S, Koido M . Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells. Cell Rep. 2017; 21(10):2661-2670. DOI: 10.1016/j.celrep.2017.11.005. View

16.

Serban M, Prestwich G . Modular extracellular matrices: solutions for the puzzle. Methods. 2008; 45(1):93-8. PMC: 2504528. DOI: 10.1016/j.ymeth.2008.01.010. View

17.

Buchmann B, Engelbrecht L, Fernandez P, Hutterer F, Raich M, Scheel C . Mechanical plasticity of collagen directs branch elongation in human mammary gland organoids. Nat Commun. 2021; 12(1):2759. PMC: 8115695. DOI: 10.1038/s41467-021-22988-2. View

18.

Emerman J, Pitelka D . Maintenance and induction of morphological differentiation in dissociated mammary epithelium on floating collagen membranes. In Vitro. 1977; 13(5):316-28. DOI: 10.1007/BF02616178. View

19.

Schutgens F, Rookmaaker M, Margaritis T, Rios A, Ammerlaan C, Jansen J . Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nat Biotechnol. 2019; 37(3):303-313. DOI: 10.1038/s41587-019-0048-8. View

20.

Taguchi A, Nishinakamura R . Higher-Order Kidney Organogenesis from Pluripotent Stem Cells. Cell Stem Cell. 2017; 21(6):730-746.e6. DOI: 10.1016/j.stem.2017.10.011. View