Abstract: TH-OR138
Endothelialization of Decellularized Porcine Kidneys Sustains In Vivo Perfusion in an Acute Porcine Model
Session Information
- Translational Research Innovations in Kidney Organoid and Bioengineered Model Systems
October 25, 2018 | Location: 4, San Diego Convention Center
Abstract Time: 05:54 PM - 06:06 PM
Category: Bioengineering
- 300 Bioengineering
Authors
- Uzarski, Joseph S., Miromatrix Medical Inc., Eden Prairie, Minnesota, United States
- Atputhanathan, Senthuran, Miromatrix Medical Inc., Eden Prairie, Minnesota, United States
- Seetapun, Dominique, Miromatrix Medical Inc., Eden Prairie, Minnesota, United States
- Holzner, Matthew L., Mount Sinai Medical Center, New York, New York, United States
- Shapiro, Ron, Mount Sinai Medical Center, New York, New York, United States
- Wadhera, Vikram, Mount Sinai Medical Center, New York, New York, United States
- Florman, Sander, Mount Sinai Medical Center, New York, New York, United States
- Ross, Jeff, Miromatrix Medical, Eden Prairie, Minnesota, United States
- Adamson, Dylan, Mount Sinai Medical Center, New York, New York, United States
Group or Team Name
- Miromatrix Medical Inc.
Background
The shortage of donor kidneys forces patients suffering from kidney failure to undergo dialysis as the only alternative to transplantation, the preferred therapy with lower morbidity and mortality rates. Recellularization of kidney extracellular matrix (ECM) scaffolds derived through decellularization is a promising strategy to produce humanized renal tissues for transplantation in a shorter time frame than donor kidneys may become available.
Methods
Porcine kidneys were decellularized via perfusion with mild detergents. The derived ECM scaffolds were repopulated with human umbilical vein endothelial cells (HUVECs) to endow the grafts with thromboresistance. Key metabolic markers were monitored to non-invasively assess cell proliferation, viability, and totality of vascular endothelialization. Re-endothelialized kidneys were functionally assessed by in vitro perfusion with heparinized porcine blood or in vivo anastomosis in an acute porcine implant. Primary epithelial cells were introduced to assess survival in co-culture.
Results
HUVECs engrafted in decellularized kidney scaffolds within both the arterial and venous vasculature. Daily metabolic analysis found that glucose consumption rate (GCR) directly correlated with graft perfusability, and grafts implanted at peak GCR (Fig 1A) sustained higher volumetric blood flow. Implanted grafts anastomosed to the porcine vasculature showed excellent perfusion of the vascular tree, as demonstrated by angiography (Fig 1B). Endothelialization sustained vascular patency during acute in vivo perfusion for up to 1 hour (Fig 1C). Co-culture of endothelialized grafts with epithelial cells showed dual survival in their respective vascular and nephron niches.
Conclusion
Effective engraftment and proliferation of human endothelial cells within porcine kidney scaffolds indicates that the renal ECM retains critical integrin adhesion sites. Sustained perfusion of endothelialized grafts during blood loops and acute implants represents an important step toward chronic transplantation of recellularized whole kidney grafts in human-scale preclinical models.
Funding
- Private Foundation Support