Abstract
PurposeArtificial organs might serve as alternative solutions for whole organ transplantation. Decellularization of a liver provides a non-immunogenic matrix with the advantage of three afferent systems, the portal vein, the hepatic artery and the bile duct. This study aims to evaluate the recellularization of rat livers with islets of Langerhans via the bile duct and the portal vein for the comparison of different perfusion routes.MethodsRat livers were decellularized in a pressure-controlled perfusion manner and repopulated with intact isolated islets of Langerhans via either the portal vein or the bile duct.ResultsRepopulation via the portal vein showed islet clusters stuck within the vascular system demonstrated by ellipsoid borders of thick reticular tissue around the islet cluster in Azan staining. After recellularization via the bile duct, islets were distributed close to the vessels within the parenchymal space and without a surrounding reticular layer. Large clusters of islets had a diameter of up to 1000 µm without clear shapes.ConclusionWe demonstrated the bile duct to be superior to the portal vein for repopulation of a decellularized rat liver with islets of Langerhans. This technique may serve as a bioengineering platform to generate an implantable and functional endocrine neo-pancreas and provide scaffolds with the anatomic benefit of three afferent systems to facilitate co-population of cells.
Highlights
Diabetes mellitus type 1 had a prevalence of 1.93 per 1000 in the US 2009 and requires life-long treatment [1]
At the end of the decellularization procedure, both groups showed a decline in DNA content compared to the control group [flow-controlled: 2.5 μg/mg (0.7–4.2); pressurecontrolled: 4.0 μg/mg (0.6–57.7); control: 124.0 μg/mg (107.8–188.5), Fig. 2]
We demonstrated the benefit of the bile duct instead of the portal vein as a repopulation route for a decellularized rat liver
Summary
Diabetes mellitus type 1 had a prevalence of 1.93 per 1000 in the US 2009 and requires life-long treatment [1]. Exogenous insulin replacement helps to regulate blood glucose levels in order to prevent vascular, renal and neurological complications. Sufficient metabolic regulation cannot be reached in some patients, and pancreas or islet transplantation may be indicated for further therapy [1–3]. Pancreas transplantation is an established procedure and predominant to islet transplantation, but bares the risk for major complications, e.g. acute rejection, post-transplantation pancreatitis and severe infections, leading to graft loss in approximately 10% of patients [4, 5]. Islet transplantation appears to be less invasive and safer [4]. Metabolic function after islet transplantation is negatively affected by hypoxia, partial portal vein
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