Abstract: SA-PO037
Prolonged In Vivo Perfusion of a Re-Endothelialized Human-Scale Tissue Engineered Kidney Graft
Session Information
- Engineering-Based Approaches to Problems in Nephrology
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bioengineering
- 300 Bioengineering
Authors
- Uzarski, Joseph S., Miromatrix Medical, Inc., Eden Prairie, Minnesota, United States
- Russell, Emily, Miromatrix Medical, Inc., Eden Prairie, Minnesota, United States
- Beck, Emily C., Miromatrix Medical, Inc., Eden Prairie, Minnesota, United States
- Holzner, Matthew L., Recanati/Miller Transplantation Institute, New York, New York, United States
- Wadhera, Vikram, Recanati/Miller Transplantation Institute, New York, New York, United States
- Shapiro, Ron, Recanati/Miller Transplantation Institute, New York, New York, United States
- Adamson, Dylan, Recanati/Miller Transplantation Institute, New York, New York, United States
- Florman, Sander, Mount Sinai Medical Center, New York, New York, United States
- Davidow, Dominique, Miromatrix Medical, Inc., Eden Prairie, Minnesota, United States
- Ross, Jeff, Miromatrix Medical, Inc., Eden Prairie, Minnesota, United States
Background
Advances are desperately needed to increase the supply of transplantable kidneys for the 100,000 patients on the waiting list. Whole organ engineering is one approach that holds tremendous promise and to date, the most successful approach utilizes perfusion decellularization to provide the ideal kidney extracellular matrix scaffold that maintains the organ’s native vasculature and architecture, and allows recellularization with human cells. A critical component and the focus of the current study is to demonstrate the ability to functionally revascularize clinically relevant whole kidney matrix with human endothelial cells and provide sustained in vivo perfusion following orthotopic implantation.
Methods
Kidneys recovered from adult pigs were decellularized via detergent perfusion through the vasculature. The porcine matrix was seeded with human umbilical vein endothelial cells (HUVECs) and cultured using a custom perfusion recellularization bioreactor until sufficient cellular coverage of the vasculature was obtained. Functional testing of the renal vascular bed was performed using an ex vivo porcine blood flow model. Re-endothelialized kidney grafts were transplanted orthotopically in a pig model and evaluated with angiography at days 3, 7, 10, and 14 days before explantation.
Results
A minimum glucose consumption rate of 20 mg/hr was determined to represent sufficient endothelialization to sustain continuous blood flow (>100 mL/min) ex vivo, and was predictive of early patency in orthotopic transplants. At 7 days after transplantation in pigs, 83.3% (n=5/6 pigs) of grafts in surviving animals maintained renal perfusion during follow-up angiography. One kidney graft remained patent through post-operative day 14.
Conclusion
As 14 days is the longest reported continuous perfusion of a revascularized kidney graft to date, these results lay the foundation for the long-term success of human-scale recellularized kidney grafts and move the field closer to increasing the supply of transplantable kidneys.
Funding
- Private Foundation Support