Introduction: Whole-organ decellularization is an attractive approach for 3D organ engineering and for studying cell-extracellular matrix interaction. However, progress of this approach is hindered by the intravascular blood coagulation that occurs after in-vivo implantation of the re-cellularized scaffold, resulting in short-term graft survival. In this study, we sought an alternative approach for 3D organ engineering through an axial pre-vascularization approach and examined its suitability for pancreatic islet transplantation.

Methods: Whole-Livers from male Lewis rats were decellularized through sequential arterial perfusion of detergents. The decellularized liver scaffold was implanted into Lewis rats and an arteriovenous bundle was passed through the scaffold. At the time of implantation, fresh bone marrow preparation (BM; n=3) or adipose-derived stem cells (ADSCs; n=4), or HBSS (n=4) was injected into the scaffold through the portal vein. After 5 weeks, around 2,600 IEQ of islets were injected through portal vein of the scaffold. The recipient rats were made diabetic by injection of 65 mg/kg STZ i.v., and were followed up by measuring blood glucose and body weight for 30 days. Intravenous glucose tolerance test was performed in the cured animals and samples were collected for immunohistochemical analysis (IHC). Micro-CT images were obtained from one rat in each group for representation.

Results: Two rats in the BM group and one rat in the ADSCs group showed normalization of blood glucose, while one rat from each group showed partial correction of blood glucose. In contrast, no rats were cured in the HBSS group. Micro-CT showed evidence of sprouting from the arteriovenous bundle inside the scaffold. IHC showed insulin-positive cells in the three groups. vWF-positive cells in the islet region were significantly higher in the BM and ADSCs groups in comparison to HBSS group. The number of BrdU-positive cells was significantly lower in the BM group in comparison to the other two groups.

Conclusion: Despite the limited numbers, the study showed the promising potential of the pre-vascularized whole-organ scaffold as a novel approach for islet transplantation. Both BM and ADSCs were superior to the acellular scaffold.