Abstract: SA-PO023
An Immunoprotective Multi-Channel Kidney Bioreactor for Implantable Renal Replacement
Session Information
- Bioengineering: Modeling, Diagnosis, Therapy
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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