Introduction

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder that results in the destruction of insulin-producing pancreatic β-cells, leading to lifelong dependence on exogenous insulin. Patients without adequate glycemic control are at risk for severe complications such as retinopathy, nephropathy, and limb amputation. For these individuals, pancreatic islet transplantation has is a promising therapeutic strategy that can restore endogenous insulin production. However, current transplantation practices typically rely on infusion of islets into the hepatic portal vein—a method associated with significant drawbacks. These include immediate blood-mediated inflammatory reactions (IBMIR), limited insulin release due to the hypoxic environment, and exposure to high levels of immunosuppressants. As a result, multiple donor pancreases are often required to achieve insulin independence, exacerbating the scarcity of donor organs. To overcome these limitations, there is growing interest in identifying alternative, extrahepatic transplantation sites that can provide a more supportive environment for islet engraftment. Human placental cotyledons, which are highly vascularized and readily available following elective cesarean deliveries, represent a novel and potentially advantageous site for islet engraftment. This study explores the feasibility of combining ex vivo placental cotyledon perfusion with islet transplantation to evaluate its potential as a new extrahepatic transplant platform.

Materials and Methods

A novel ex vivo perfusion system for human placental cotyledons was developed through iterative design, focusing on sterility, vasospasm prevention, and optimized tubing. Postcesarean placentas were used to isolate and perfuse a single cotyledon under controlled conditions. After four hours, human pancreatic islets were injected into the intervillous space. Islet function was assessed the next day by a glucose-stimulated insulin secretion (GSIS) measurement as well as functional measurements.

Results

The perfusion setup maintained stable physiological conditions over 23 hours. Insulin secretion increased during high-glucose, showing viable and functional islets after 14 hours of perfusion. Insulin was detected in cotyledon effluent but not fetal venous return, likely due to perfusion flow and placental barriers. Conclusion The 23-hour perfusion demonstrated effective function without infection or tissue damage. Injected islets remained viable and glucose-responsive in the intervillous space. While the setup met several criteria for evaluating extrahepatic transplantation sites, further research is needed to address leakage from the cotyledon and to investigate changes in hormonal secretion of the cotyledon during long-term perfusion.