IP Library › Granted Patent US 12,281,333
Granted Patent B2
US 12,281,333 · App. 17/518,395 · Granted Apr 22, 2025

Renal tube assay device and methods of manufacture and use

Inventors: Andras Czirok (Roeland Park, KS); Pamela Tran (Overland Park, KS)
Assignee: UNIVERSITY OF KANSAS
C12N5/0686C12M23/06C12M23/16C12M41/36C12M41/46G01N33/5044
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Quick Facts
Patent No.
US 12,281,333
App. No.
17/518,395
Granted
Apr 22, 2025
Kind
B2
Abstract

A renal tube assay device can include: a container having an inlet port and an outlet port; a matrix material in the container; and a lumen in the matrix material extending from the inlet port to the outlet port. The lumen can include a luminal surface with at least one low density region that has a lower density compared to another adjacent region of the matrix material that is located at least partially around the at least one low density region. The low density region can have a form of a bubble, bulge, capsule, or the like. The low density region can bulge into the lumen. A port can be adapted for receiving a pipette tip. The matrix material can include a hydrogel. The container can be located in a cell culture dish.

Claims (39)

1. A renal tube assay device comprising:

a container having an inlet port and an outlet port;

a matrix material in the container, therein the container is located in a cell culture dish; and

a lumen in the matrix material extending from the inlet port to the outlet port,

wherein the lumen includes a luminal surface with at least one low density region that has a lower density compared to another adjacent region of the matrix material that is located at least partially around the at least one low density region.

2. The renal tube assay device of claim 1 , wherein the at least one low density region has a form of a bubble.

3. The renal tube assay device of claim 1 , wherein the inlet port and/or outlet port is adapted for receiving a pipette tip.

4. The renal tube assay device of claim 1 , wherein the matrix material includes a hydrogel.

5. The renal tube assay device of claim 1 , wherein the low density region bulges into the lumen.

6. The renal tube assay device of claim 1 , comprising a cell culture in the lumen.

7. The renal tube assay device of claim 1 , comprising a cell culture in the at least one low density region, thereby forming a bulge structure.

8. The renal tube assay device of claim 1 , comprising a renal cell culture in the lumen with cells in the at least one low density region, thereby forming a bulge structure.

9. A renal tube assay system comprising:

the renal tube assay device of claim 1 ; and

a fluidic flow system including at least one pump fluidly coupled with at least one of the inlet port or outlet port wherein the at least one pump is coupled with a conduit that extends into a cell culture dish having the renal tube assay device in cell culture media.

10. The renal tube assay system of claim 9 , further comprising an analytical system operably coupled with the lumen in the matrix material.

11. The renal tube assay system of claim 10 , wherein the analytical system is an optical system having at least one optical device configured for acquiring images or video of the lumen.

12. The renal tube assay system of claim 9 , further comprising a rotational system having a rotational mechanism coupled to the container such that the container rotates with rotation of the rotational mechanism.

13. A method of forming a bulge cell culture in a renal tube construct, comprising:

providing the renal assay system of claim 9 , and therein and culturing renal cells in the lumen and in the at least one low density region to form a bulge in the matrix material with the renal cells.

14. The method of claim 13 , comprising rotating the container and matrix material to rotate the lumen and renal cells therein.

15. A method of studying a bulge cell culture in a renal tube construct, comprising:

providing the renal assay system of claim 9 , and therein:

culturing renal cells in the lumen and in the at least one low density region to form a bulge in the matrix material with the renal cells;

pumping a media fluid through the lumen; and

monitoring the cells in the lumen and bulge.

16. The method of claim 15 , wherein the monitoring is optical monitoring with an optical system.

17. A method of studying activity of an agent in a renal tube construct, comprising:

providing the renal assay system of claim 9 , and therein:

culturing renal cells in the lumen and in the at least one low density region to form a bulge in the matrix material with the renal cells;

pumping a media fluid containing the agent through the lumen; and

monitoring the cells in the lumen and bulge.

18. A method of forming the renal tube assay device of claim 1 , comprising:

forming a container having an inlet port and an outlet port;

forming a matrix material in the container around a lumen material, wherein the matrix material is formed to include at least one low density region that has a lower density compared to another adjacent region of the matrix material that is located at least partially around the at least one low density region;

vortexing or bubbling a gas through the matrix material during formation; and

withdrawing the lumen material to form a lumen in the matrix material extending from the inlet port to the outlet port, wherein the lumen includes a luminal surface with at least one of the low density regions.

19. The method of claim 18 , comprising culturing renal cells in the lumen and in the at least one low density region to form a bulge in the matrix material with the renal cells.

20. The method of claim 19 , comprising rotating the container and matrix material to rotate the lumen and renal cells therein.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 3, 2021
From: CZIROK, ANDRAS; TRAN, PAMELA
To: THE UNIVERSITY OF KANSAS
Reel/Frame 058011/0928 →
Continuity (2)
Provisional Application 63109630 · Nov 4, 2020
Related Publication 20220135951A1 · May 5, 2022
References Cited (35)
US 10702630B2 · Lewis · 2020 [cited by examiner]
US 20150087004A1 · Chen · 2015 [cited by examiner]
US 20170009194A1 · Golway · 2017 [cited by examiner]
Supplemental Information for Homan et al. 2016. “Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips”. Sci Rep 6, 34845. 13 pages total. https://doi.org/10.1038/srep34845 (Year: 2016). [cited by examiner]
Sullivan et al. 1998. “Epithelial transport in polycystic kidney disease”. Physiological reviews, 78(4), pp. 1165-1191. https://doi.org/10.1152/physrev. 1998.78.4.1165 (Year: 1998). [cited by examiner]
Homan et al. 2016. “Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips”. Sci Rep 6, 34845. 13 pages total, https://doi.org/10.1038/srep34845 (Year: 2016). [cited by examiner]
Jiménez-Torres et al. 2016. “LumeNEXT: a practical method to pattern luminal structures in ECM gels”. Advanced healthcare materials, 5(2), p. 198-204; doi: 10.1002/adhm.201500608 (Year: 2020). [cited by examiner]
Rein et al. 2020. “Effect of luminal flow on doming of mpkCCD cells in a 3D perfusable kidney cortical collecting duct model”. American Journal of Physiology-Cell Physiology, 319(1), pp. C136-C147 (Year: 2020). [cited by examiner]
Koslowski et al.; “An Overview of In Vivo and In Vitro Models for Autosomal Dominant Polycystic Kidney Disease: A Journey from 3D-Cysts to Mini Pigs”; whitepaper; Int. J. Mol. Sci. 2020, 21(12), 4537; Published Jun. 25,… [cited by applicant]
Sharma et al.; “In vitro cyst formation of ADPKD cells, Chapter 5”; Book; Methods in Cell Biology; vol. 153, pp. 93-111, 2019; doi: 10.1016/bs.mcb.2019.05.008. [cited by applicant]
Belmonte et al.; “Virtual-tissue computer simulations define the roles of cell adhesion and proliferations in the onset of kidney cystic disease”; Mol Biol Cell; 27(22); Nov. 7, 2016; 13 pages. [cited by applicant]
Bielmeier C, Alt S, Weichselberger V, et al.; “Interface Contractility between Differently Fated Cells Drives Cell Elimination and Cyst Formation”; Current Biology; 2016; 26(5): pp. 563-574; doi: 10.1016/j.cub.2015.12.0… [cited by applicant]
Sun, Y. et al.; “Drug discovery for polycystic kidney disease”; Acta Pharmacol Sin 32; 12 pages; Jun. 3, 2011; doi: 10.1038/aps.2011.29. [cited by applicant]
Liu B et al.; “Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease”; BMC Nephrol; 13:109; Published Sep. 11, 2012; doi:10.1186/1471-2369-13-109. [cited by applicant]
Mangoo-Karim, R. et al.; “Renal epithelial cyst formation and enlargement in vitro: Dependence on cAMP”; Proc. Nat. Acad. Sci USA; vol. 86. pp. 6007-6011; Aug. 1989. Physiological Sciences. [cited by applicant]
Zanetti F.; “Organ-on-a-chip, Engineered Microenvironments for Safety and Efficacy Testing, Chapter 7”; 2020; pp. 233-253; ISBN: 978-0-12-817202-5, doi: 10.1016/C2018-0-01892-7. [cited by applicant]
Schutgens, F., et al.; “Tubuloids derived from human adult kidney and urine for personalized disease modeling”; Nature Biotechnology, vol. 37, 2019; pp. 303-331; DOI:10.1038/s41587-019-0048-8. [cited by applicant]
Homan Ka et al. “Flow-enhanced vascularization and maturation of kidney organoids in vitro”; Nat Methods; Mar. 16, 2019; 16(3): pp. 255-262; doi:10.1038/s41592-019-0325-y. [cited by applicant]
Lin, Neil Y. C. et al.; “Renal reabsorption in 3D vascularized proximal tubule models”; Proceedings of the National Academy of Sciences; Mar. 2019; 116 (12); pp. 5399-5404; DOI: 10.1073/pnas.1815208116. [cited by applicant]
Lee et al.; “Kidney-on-a-Chip: A New Technology for Predicting Drug Efficacy, Interactions, and Drug-Induced Nephrotoxicity”; Current Drug Metabolism, 2018, 19, pp. 577-583; Accepted Nov. 12, 2017; doi: 10.2174/13892002… [cited by applicant]
Cruz Nelly M et al.; “Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease”; Nat Mater.; Nov. 2017 ;16(11): pp. 1112-1119; doi: 10.1038/nmat4994. [cited by applicant]
Weber EJ et al.; “Development of a microphysiological model of human kidney proximal tubule function”; Kidney Int. 2016; 90(3); pp. 627-637; doi:10.1016/j.kint.2016.06.011. [cited by applicant]
Homan, K. et al.; “Bioprinting of 3D Convoluted Renal Proximal Tubules on Perfusable Chips”; Sci Rep 6, 34845; Oct. 11, 2016; 13 pages; https://doi.org/10.1038/srep34845. [cited by applicant]
Jang, K., & Suh, K.Y.; “A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells”; Lab Chip; Jan. 7, 2021 10(1), pp. 36-42; doi 10.1039/b907515a. [cited by applicant]
Baudoin, Régis et al.; “Development of a Renal Microchip for In Vitro Distal Tubule Models”; Biotechnology progress. 23. pp. 1245-53. Doi:10.1021/bp0603513. [cited by applicant]
Rein et al.; “Effect of Luminal Flow on Doming of mpkCCD cells in a 3D perfusable kidney cortical collecting duct model”; Am J Physiol Cell Physiol 319:C136-C147; 2020; doi: 10.1152/ajpcell.00405.2019. [cited by applicant]
Chapron et al.; “An Improved Vascularized, Dual-Channel Mircophysiological system Facilities Modeling of Proximal Tubular Solute Secretion”; ACS Pharmacol Transl. Sci.; 2020; 2, pp. 496-508; doi: 10.1021/acsptsci.9b0007… [cited by applicant]
Cai et al.; “A RhoA-YAP-c-Myc signaling axis promotes the developments of polycystic kidney disease”; Genes Dev. Jun. 1, 2018;32(11-12):781-793. doi: 10.1101/gad.315127.118. Epub Jun. 11, 2018. PMID: 29891559; PMCID: PM… [cited by applicant]
Cordido A. et al.; “The Genetic and Cellular Basis of Autosomal Dominant Polycystic Kidney Disease—A Primier for Clinicians”; Front Pediatr. Dec. 18, 2017;5:279. doi: 10.3389/fped.2017.00279. PMID: 29326913; PMCID: PMC5… [cited by applicant]
Formica, C et al.; “Molecular pathways involved in injury repair and ADPKD progression”; Cell Signal. Aug. 2020; 72:109648; doi: 10.1016/j.cellsig.2020.109648; Epub Apr. 19, 2020; PMID: 32320858. [cited by applicant]
Miceli, C. et al.; The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells; Nat Cell Biol 22, 1091-1102 (2020). doi: 10.1038/s41556-020-0566-0. [cited by applicant]
Nigro, E. et al.; “Polycystin-1 Regulates Actomyosin Contraction and the Cellular Response to Extracellular Stiffness”; Sci Rep. Nov. 12, 2019;9(1):16640. doi: 10.1038/s41598-019-53061-0. PMID: 31719603; PMCID: PMC68511… [cited by applicant]
Nigro, E. et al.; “Role of the polycystins as mechanosensors of extracellular stiffness”; Am J Physiol Renal Physiol. May 1, 2021;320(5):F693-F705. doi: 10.1152/ajprenal.00545.2020. Epub Feb. 22, 2021. PMID: 33615892. [cited by applicant]
Nishimura, R. et al.; “Solo and Keratin Filaments Regulate Epithelial Tubule Morphology”; Cell Struct Funct. Jun. 2, 2018;43(1):95-105. doi: 10.1247/csf.18010. Epub Apr. 28, 2018. PMID: 29709890. [cited by applicant]
Stoos, B. et al.; “Characterization of a mouse cortical collecting duct cell line”; Kidney Int. Jun. 1991;39(6):1168-75. doi: 10.1038/ki.1991.148. PMID: 1654478. [cited by applicant]