Whole organ sheep kidney tissue engineering and in vivo transplantation: Effects of perfusion-based decellularization on vascular integrity.

Introduction: During the past decade, increased efforts have been made to develop alternative management options instead of dialysis and homograft renal transplantation for end-stage renal disease. State-of-the-art methods employ tissue engineering to produce natural acellular scaffolds that could resolve the concern of allograft rejection and obviate the need for immunosuppressive therapy. Complete decellularization of kidney with intact extracellular matrix is crucial for in vivo compatibility and success of transplantation. Herein, we evaluate the efficacy of two different whole organ decellularization protocols, vasculature integrity, and in vivo transplantation of sheep kidneys.

Materials And Methods: Eight sheep kidneys were decellularized by perfusion-based method utilizing two different protocols (Protocol 1: 1% Triton X-100 and 0.5% SDS vs. Protocol 2: 1% SDS). The samples were evaluated by histopathology in terms of decellularization and extracellular matrix preservation. Computerized tomography angiography was performed to evaluate vasculature. Subsequently, both methods were transplanted in four sheep and monitored for vascular integrity and extravasations in short-term.

Results: Scaffolds obtained from both protocols were entirely decellularized. However; the extracellular matrix was better preserved in protocol 1 compared to protocol 2. In addition, the vascular integrity was intact in decellularized scaffolds treated with Triton X-100 plus SDS (protocol 1). After transplantation, the samples treated with protocol 2 showed extravasation of fluid in the interstitial space while the samples treated with protocol 1 showed intact extracellular matrix and vasculature.

Conclusions: This study demonstrated the efficacy of well-preserved acellular scaffold and vasculature network in post renal transplant outcome in a sheep model. These results have potential to pave the road for further investigations in acellular whole organ transplantation.