• 1.

    Lawlor KT, et al. Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation. Nat Mater 2021; 20:260271. doi: 10.1038/s41563-020-00853-9

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Czerniecki SM, et al. High-throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping. Cell Stem Cell 2018; 22:929940.e4. doi: 10.1016/j.stem.2018.04.022

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Freedman BS. A commercially available kit to generate human kidney organoids. (Re)Building a Kidney, University of Washington, 2021. https://www.rebuildingakidney.org/id/17-EBYM

    • Search Google Scholar
    • Export Citation
  • 4.

    Ryan AR, et al. Vascular deficiencies in renal organoids and ex vivo kidney organogenesis. Dev Biol 2021; 477:98116. doi: 10.1016/j.ydbio.2021.04.009

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Homan KA, et al. Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat Methods 2019; 16:255262. doi: 10.1038/s41592-019-0325-y

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    van den Berg CW, et al. In vivo assessment of size-selective glomerular sieving in transplanted human induced pluripotent stem cell-derived kidney organoids. J Am Soc Nephrol 2020; 31:921929. doi: 10.1681/ASN.2019060573

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Nam SA, et al. Graft immaturity and safety concerns in transplanted human kidney organoids. Exp Mol Med 2019; 51:113. doi: 10.1038/s12276-019-0336-x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Taguchi A, Nishinakamura R. Higher-order kidney organogenesis from pluripotent stem cells. Cell Stem Cell 2017; 21:730746.e6. doi: 10.1016/j.stem.2017.10.011

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Uchimura K, et al. Human pluripotent stem cell-derived kidney organoids with improved collecting duct maturation and injury modeling. Cell Rep 2020; 33:108514. doi: 10.1016/j.celrep.2020.108514

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Tanigawa S, et al. Generation of the organotypic kidney structure by integrating pluripotent stem cell-derived renal stroma. Nat Commun 2022; 13:611. doi: 10.1038/s41467-022-28226-7

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Helms L, et al. Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations. JCI Insight 2021; 6:e154882. doi: 10.1172/jci.insight.154882

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Jansen J, et al. SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids. Cell Stem Cell 2022; 29:217231.e8. doi: 10.1016/j.stem.2021.12.010

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    • Search Google Scholar
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Organoids Advance Kidney Science

Hongxia FuHongxia Fu, PhD, and Benjamin S. Freedman, PhD, are faculty in the Divisions of Hematology and Nephrology, respectively, Department of Medicine and Kidney Research Institute, University of Washington School of Medicine, Seattle.

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Benjamin S. FreedmanHongxia Fu, PhD, and Benjamin S. Freedman, PhD, are faculty in the Divisions of Hematology and Nephrology, respectively, Department of Medicine and Kidney Research Institute, University of Washington School of Medicine, Seattle.

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Ten years ago, human kidney organoids were but twinkles in the eyes of a few intrepid inventors. Now, these tiny collections of cells, which bear a striking resemblance to kidney tissue, are well on their way to becoming a standard research tool. As they spread, kidney organoids are also becoming more diverse and gaining new abilities.

The ability of organoids to mimic features of kidney diseases presents new opportunities to discover medications and exciting possibilities for regenerative medicine. To generate the structures more reproducibly and optimize their shapes and sizes, a technique, called cellular extrusion bioprinting, has recently been introduced in which organoid progenitor cells are “printed” in specific patterns (1). Similarly, automated instruments (robots) capable of performing routine cell-culture tasks can be harnessed to produce large batches of organoids in microwell-plate formats for querying hundreds of conditions simultaneously (2). Generating organoids in the lab used to require substantial expertise, but now researchers can purchase a commercially available kit to grow organoids (just add cells) (3). These advances increase the scale and reproducibility of kidney organoid technology.

Organoids naturally contain blood vessel endothelial cells, but these fail to link with the podocytes to form glomeruli and may die over time (2, 4). This endothelium can be increased by treating organoids with vascular endothelial growth factor (2, 4) or by flowing media over the organoids in a microfluidic chamber (5). The most exciting findings, however, are seen when human organoids are implanted beneath the kidney capsule of living mice. Blood vessels from the mice invade the organoid podocytes to produce glomerulus-like structures, which can “sieve” high molecular weight carbohydrates from the blood (4, 6, 7).

The “original” kidney organoids were limited to proximal nephron structures containing podocytes, proximal tubules, and distal tubules in connected segments. Subsequent work described methods to produce structures that resemble primitive collecting ducts, which were combined with the original organoids to produce “higher order” structures (8, 9). The addition of a third population of cells to the mix that represents supporting, connective tissue-like cells similar to those found in the renal interstitium appears to encourage the collecting duct-like structures to grow and branch, at least in mouse organoids, resulting in striking images (Figure 1) (10).

Figure 1
Figure 1

Higher order organoid (0.5 mm diameter) after implantation into a mouse host

Citation: Kidney News 14, 4

How are kidney organoids currently being used? COVID-19 provides a case in point. In the midst of the pandemic, kidney organoids emerged as powerful models for studying SARS-CoV-2 infection and its potential treatments. A trend in these recent studies is cross-validation of data from organoids with data from clinical cohorts (11, 12). This fruitful back-and-forth produces a more holistic understanding than could be ascertained from either system on its own and is likely to be a common theme as this technology matures.

With advances being made at both the vascular and ureteric ends of the nephron, organoids are rapidly evolving (Figure 2). This evolution presents untapped opportunities to study a variety of kidney disorders and potentially to regrow parts of kidney tissues from autologous cells. A key question is whether organoids can perform kidney functions. It is not yet clear whether organoid grafts have any therapeutic benefit. They also contain fast-growing immature cells that could turn into tumors (7). The next few years will likely prove pivotal in our understanding of these issues as organoids inch closer to the real thing.

Figure 2
Figure 2

Evolution of organoids

Citation: Kidney News 14, 4

References

  • 1.

    Lawlor KT, et al. Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation. Nat Mater 2021; 20:260271. doi: 10.1038/s41563-020-00853-9

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Czerniecki SM, et al. High-throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping. Cell Stem Cell 2018; 22:929940.e4. doi: 10.1016/j.stem.2018.04.022

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Freedman BS. A commercially available kit to generate human kidney organoids. (Re)Building a Kidney, University of Washington, 2021. https://www.rebuildingakidney.org/id/17-EBYM

    • Search Google Scholar
    • Export Citation
  • 4.

    Ryan AR, et al. Vascular deficiencies in renal organoids and ex vivo kidney organogenesis. Dev Biol 2021; 477:98116. doi: 10.1016/j.ydbio.2021.04.009

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Homan KA, et al. Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat Methods 2019; 16:255262. doi: 10.1038/s41592-019-0325-y

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    van den Berg CW, et al. In vivo assessment of size-selective glomerular sieving in transplanted human induced pluripotent stem cell-derived kidney organoids. J Am Soc Nephrol 2020; 31:921929. doi: 10.1681/ASN.2019060573

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Nam SA, et al. Graft immaturity and safety concerns in transplanted human kidney organoids. Exp Mol Med 2019; 51:113. doi: 10.1038/s12276-019-0336-x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Taguchi A, Nishinakamura R. Higher-order kidney organogenesis from pluripotent stem cells. Cell Stem Cell 2017; 21:730746.e6. doi: 10.1016/j.stem.2017.10.011

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Uchimura K, et al. Human pluripotent stem cell-derived kidney organoids with improved collecting duct maturation and injury modeling. Cell Rep 2020; 33:108514. doi: 10.1016/j.celrep.2020.108514

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Tanigawa S, et al. Generation of the organotypic kidney structure by integrating pluripotent stem cell-derived renal stroma. Nat Commun 2022; 13:611. doi: 10.1038/s41467-022-28226-7

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Helms L, et al. Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations. JCI Insight 2021; 6:e154882. doi: 10.1172/jci.insight.154882

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Jansen J, et al. SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids. Cell Stem Cell 2022; 29:217231.e8. doi: 10.1016/j.stem.2021.12.010

    • Crossref
    • Search Google Scholar
    • Export Citation
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