Islet Transplantation in the Lung via Endoscopic Aerosolization: Investigation of Feasibility, Islet Cluster Cell Vitality, and Structural Integrity

Abstract

Aerosolized drug delivery has recently attracted much attention as a possible new tool for the delivery of complex nanoparticles. This study aims to investigate whether catheter-based aerosolization of islets via endobronchial systems is a feasible option in islet transplantation. Besides investigating the feasibility of islet aerosolization, we also examined cluster cell vitality and structural integrity of the islets following aerosolization. Using an ex vivo postmortem swine model, porcine pancreatic islets were isolated and aerosolized with an endoscopic spray catheter. Following aerosolization, islet cell vitality and function were assessed via Calcein AM and propidium iodide as well as insulin production after glucose exposure. In the final step, the overall feasibility of the procedure and structural integrity of cells were analyzed and evaluated with respect to clinical applicability. No significant difference was detected in the viability of control islets (90.67 ± 2.19) vs aerosolized islets (90.68 ± 1.20). Similarly, there was no significant difference in control islets (1.62 ± 0.086) vs aerosolized islets (1.42 ± 0.11) regarding insulin release after stimulation. Indocyanine green marked islets were transplanted into the lung without major difficulty. Histological analysis confirmed retained structural integrity and predominant location in the alveolar cavity. Our ex vivo data suggest that catheter-based aerosolized islet cell delivery is a promising tool for the application of cell clusters. According to our data, islet cell clusters delivery is feasible from a mechanical and physical perspective. Moreover, cell vitality and structural integrity remain largely unaffected following aerosolization. These preliminary results are encouraging and represent a first step toward endoscopically assisted islet cell implantation in the lung.

Exploring Insulin Production Following Alveolar Islet Transplantation (AIT)

“…To the authors’ knowledge, no attempts have been made to investigate actual islet transplantation in the lung by means of aerosolization except for one study which discussed the potential of such a concept [ 10 ]. Endoscopically assisted AIT could reduce complication rates, dosing errors, as well as the need for repetitive inhalations as compared to inhaled insulin.…”

“…While bronchoscopy is not completely risk-free, the occurrence of severe complications is still considered rare [ 28 , 29 ]. Aerosolization of islets while preserving their mechanical stability has been previously demonstrated as technically feasible [ 10 ]. However, there are no data on the behavior of islets following AIT from an anatomical and physiological perspective.…”

“…Moreover, with a wide range of potential implantation sites, it is quite a challenge to choose an optimal location with respect to the aforementioned challenges. As demonstrated in a recent study, islets can potentially be implanted within the alveolar space by means of aerosolization [ 10 ]. In recent years, the scientific community has expressed increased interest in aerosol-based and catheter-guided medical and pharmacological applications [ 11 , 12 , 13 , 14 ].…”

“…Alveolar islet transplantation (AIT) is a new promising concept with the potential to overcome the problem of oxygen deprivation and distance to the vascular network while providing islets with nutritional supply. Until today, specific technical and applicational aspects for the transplantation have barely been studied [ 10 ]. By means of a swine lung model, this study aims to analyze islet cell distribution and as well as the extent of insulin production at the transplantation site following AIT.…”