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Kidney Week

Abstract: PO0306

Human Amniotic Membrane as a Novel Scaffold for Induced Pluripotent Stem Cell-Derived Kidney Organoids

Session Information

  • Bioengineering
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

  • 300 Bioengineering

Authors

  • Figetakis, Maria, Yale University, New Haven, Connecticut, United States
  • James, Kevin J., Yale University, New Haven, Connecticut, United States
  • Torres, Richard, Yale University, New Haven, Connecticut, United States
  • Chang, William Gee, Yale University, New Haven, Connecticut, United States
Background

Human inducible pluripotent stem cells (hiPSCs) can be differentiated into kidney organoids that could be used to tissue-engineer functional renal tissue. However, there are several challenges to therapeutic implementation. Among these is how to deliver organoids in a manner that would allow for both vascularization and filtrate outflow. Previous research has demonstrated in animal models, that kidney organoids can be perfused when implanted in the kidney subcapsular space. One limitation though is that there is no obvious filtrate outflow tract. Furthermore, in ESRD patients there would likely be significant fibrosis or even cystic disease that would prevent successful perfusion and filtrate outflow of kidney organoids implanted in a similar manner. Alternative heterotopic organoid implantation strategies should be considered. Examples include, but are not limited to, peritoneal implantation (with peritoneal dialysis catheter drainage) or tissue engineered tubular constructs for ureteral anastomoses. Here we describe a biomaterial, decellularized human amniotic membrane (dhAM), that could be used for differentiation of iPSC derived kidney organoids. Because kidney organoids will be exposed to mechanical forces in heterotopic implant locations, we examine the effects of uniaxial stretch on the structure of kidney organoid tubules.

Methods

We decellularized hAM with mild detergents, and differentiated kidney organoids in a manner previously described by the Little research group. We constructed a titanium stretch device that allowed for kidney organoid differentiation and uniaxial stretch of the dhAM acutely or over 10 days. We performed multiphoton microscopy to image the kidney organoids and then used 3D reconstructions to measure tubular volumes.

Results

We have observed that iPSC-derived kidney organoids can be differentiated on dhAM, and that uniaxial stretch of the dhAM elongates and increases tubular volumes within the kidney organoids, without tubular disruption or increased cell death.

Conclusion

dhAM is a promising scaffold for studying effects of mechanical forces on human kidney organoids in vitro. dhAMs could be used to facilitate the implantation of kidney organoids into the peritoneum or other heterotopic locations. The constructs have the flexibility to be used as a patch, modified into tubes after rolling, or form saclike structures.

Funding

  • Other NIH Support