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Abstract: SA-PO023

An Immunoprotective Multi-Channel Kidney Bioreactor for Implantable Renal Replacement

Session Information

Category: Bioengineering

  • 400 Bioengineering

Authors

  • Torres, Alonso, University of California San Francisco, San Francisco, California, United States
  • Porock, Edward, University of California San Francisco, San Francisco, California, United States
  • Blaha, Charles, University of California San Francisco, San Francisco, California, United States
  • Wright, Nathan, University of California San Francisco, San Francisco, California, United States
  • Sorrentino, Thomas, University of California San Francisco, San Francisco, California, United States
  • Kim, Eun jung, University of California San Francisco, San Francisco, California, United States
  • Chen, Caressa, University of California San Francisco, San Francisco, California, United States
  • Haniff, Tariq M., University of California San Francisco, San Francisco, California, United States
  • Chui, Benjamin W., University of California San Francisco, San Francisco, California, United States
  • Moyer, Jarrett, University of California San Francisco, San Francisco, California, United States
  • Brakeman, Paul R., University of California San Francisco, San Francisco, California, United States
  • Humes, H. David, University of Michigan, Ann Arbor, Michigan, United States
  • Fissell, William Henry, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Roy, Shuvo, University of California San Francisco, San Francisco, California, United States
Background

Clinical renal replacement therapy for end-stage renal disease should replace the kidney’s filtration function and vital endocrine role. Our group engineered single-channel macroencapsulation devices housing silicon nanopore membranes (SNM) to act as renal proximal tubule epithelial cell (RPTEC) bioreactors and implanted these subclinical-scale devices in swine. To approach clinical efficacy, we are developing a scalable multi-channel design of blood-interfacing SNM bioreactors to house increased renal cell mass.

Methods

SNM with an average pore size of 7 nm and total surface area of 21 cm2 covered with thin Al2O3 coatings were plasma bonded in alternating four-channel stack pattern. The stacks were incorporated into polycarbonate housings. Cell inserts were machined from acrylic, epoxied to porous transwell membranes, seeded with 500,000 human RPTEC/cm2, and inserted into ultrafiltrate chambers of the SNM stack on the opposite side of the blood flow path. Bioreactors (n=3) were anastomosed to iliac vessels and implanted into the retroperitoneum of Yucatan minipigs. No immunosuppression or therapeutic anticoagulation was administered. Vascular angiograms using contrast were performed after a week prior to explant. Live/dead imaging of RPTEC as well as ammonia and calcitriol concentrations were measured from the ultrafiltrate chambers and pig plasma via enzyme-linked immunosorbent assays.

Results

There were no technical complications from the implants and devices were patent at explant. Angiograms showed rapid transit of contrast through the multi-channel bioreactors 7 days after implant. Live/dead imaging showed comparable cell viability in the bioreactor compared to in-vitro controls (61.0±5.70% vs 56.0±9.10%). Ammonia concentrations were similar in the pig plasma and bioreactor ultrafiltrate (0.35±0.01E-2 vs 0.36±1.00E-3 mM). Levels of calcitriol were decreased compared to pig plasma (48.0E2±93.0 vs 172.0±21.0 pg/mL).

Conclusion

We demonstrated successful implantation of multi-channel bioreactors with RPTEC for 7 days despite no immunosuppression or anticoagulation. Future directions include improving RPTEC viability and function, conducting a longer temporal study, and scaling up to larger multi-channel devices.

Funding

  • Other NIH Support